Endocrinology

The Endocrine System

endocrine-pic

The endocrine glands (ductless) secrete hormones directly into the bloodstream. Hormones are complex chemical “messengers”; they are released in tiny amounts, yet they can produce dramatic changes in the activity of body cells (high efficacy). In this way they control basic body functions such as growth, metabolism and sexual development; they are also responsible for maintaining the correct levels in the blood of certain vital substances (e.g electrolytes).

Hormones can be released into the bloodstream in a number of different ways. They may be released directly by a secreting cell, or when such a cell is stimulated by a nerve impulse. In the posterior lobe of the pituitary, nerve fibres themselves release hormones directly into the blood, which stimulate another hormone-producing cell. The following diagrams will explain further:

Endo-para-autocrine

The anterior pituitary has a rich network of blood vessels connecting it to the hypothalamus. “neurosecretions” from the hypothalamus stimulate the hormone-secreting cells.

the secretion of hormones is controlled by a complex feedback mechanism in which the nervous system is closely involved. The hypothalamus and pituitary play particularly important roles.

The pituitary gland (right) is situated at the base of the brain and is about the size of a pea; it is divided into lobes. It is subject to the influence of the hypothalamus, to which it is connected by a slender stalk. It releases a variety of hormones which act on several “target” organs. The hormones of the anterior lobe, with the exception of somatotrophin and MSH, stimulate other glands. The hypothalamus monitors the level of the hormones released by these glands and instructs the pituitary to cut off the stimulating hormone once the correct level is achieved.

The pancreas, which lies behind and under the stomach, is a mixed-function gland; as well as containing cells which secrete digestive enzymes, it has clumps of cells known as the “islets of Langerhans” which secrete hormones. These are most numerous toward the tail or pointed end of the pancreas. the islets contain two types of cells; alpha and beta. The alpha cells produce the hormone glucagon, which raises blood sugar level; the beta cells secrete insulin, which lower blood sugar level. A lack of insulin as a result of disease or damage to the pancreas results in diabetes.

The thyroid gland is situated at the base of the neck on either side of the trachea, just below the larynx. It is made up of follicles containing a fluid called colloid, in which the two thyroid hormones thyroxine and triiodothyronine (T4 and T3) are stored for release into the bloodstream as necessary. these hormones control the body’s metabolic rate. There are four small parathyroid glands situated behind the thyroid. These secrete parathyroid hormone, which primarily controls phosphorous and calcium levels in the blood.

The adrenal glands produce a variety of hormones. The adrenal cortex (outer part) is stimulated by the pituitary hormone ACTH; it it secretes a number of essential steroid hormones e.g cortisol, aldosterone and adrenal androgens.

The adrenal medulla (inner part) is entirely separate in function from the cortex and is not influenced by the pituitary gland. It secretes adrenalin and noradrenalin in response to fear, anger or sexual desire; these prepare the body for instant action by increasing the heart rate and the blood supply to the muscles.

The tubules of the testes contain cells called spermatocytes which, under the influence of gonadotropic hormones, mature into spermatozoa. These are stored in the tubules and epididymis until they are conducted to the penis at ejaculation by the vas deferens. the interstitial cells between the tubules also produce the male hormone testosterone, responsible for secondary sexual characteristics.

Acetylcholine

Acetylcholine is a vital brain neurotransmitter. Your mind slows down if it’s running low on acetylcholine (ACh). The majority of human cells (especially epithelial cells) synthesize ACh. ACh is needed for the proper functioning of cells and helps maintain homeostasis. ACh may play a role in non-neuronal function i.e. in bodily organs or systems other than the central or peripheral nervous systems.

ACh levels are regulated by acetylcholinesterase (AChE), the enzyme that nature designed to attack and destroy acetylcholine.

ACh deficiency is characteristic of Alzheimer’s disease and other age-related cognitive impairments. Treatment involves the administration of agents that inhibit the action of AChE. One such agent is galantamine.

Adrenalin (Epinephrine)

Adrenalin is the “fight or flight” hormone (because of the feeling you get during an adrenalin surge) and acts as a neurotransmitter.

Adrenalin plays a central role in the short-term stress reaction; the physiological response to conditions that threaten the physical integrity of the body. It is secreted by the adrenal medulla. When released into the bloodstream, adrenalin causes many diverse occurrences by binding to multiple receptors in the body. It acts to increase heart rate and strength of contractions, dilate the pupils and constriction of blood flow restricts blood flow in arterioles in the skin and gut. Vessels dilate in the arterioles of the leg muscle. It breaks down glycogen and synthesises glucose in the liver cells for energy, and at the same time, begins the breakdown of lipids in fat cells. It also elevates the blood sugar level (by increased hydrolysis of glycogen to glucose) and causes blood to flow away from the skin and inner organs.

Adrenalin binds to the “beta-adrenergic” receptors of the liver and muscle cells. This activates ”adenylate cyclase”, which causes glycogen breakdown.

It also binds to “alpha-1” receptors of liver cells, which activate inositol-phospholipid signalling pathway, signalling the phosphorylation of insulin, leading to reduced ability of insulin to bind to bodily receptors.

Chemokines

Chemokines are intracellular (inside the cell) messenger molecules (hormones) secreted by “CD8+” cells whose major function is to attract immune cells (like T-Cells) to sites of infection.

Dihydrotestosterone (DHT)

Dihydrotestosterone is the hormone formed in the prostate gland, testes, hair follicles and adrenal glands when the enzyme 5-alpha reductase acts on testosterone. DHT has approx. 4 times more androgen potency than testosterone. Traditionally considered a “male hormone”, DHT is also produced by females in much smaller quantities.

DHT is suspected to be a strong contributing factor in many cases of male baldness. The drug Propecia reduces the activity of 5-alpha reductase and has been used a counter against this presumed cause of baldness.

DHEA

DHEA (dehydroepiandrosterone) is produced in the adrenal glands from pregnenolone and eventually converted into testosterone, estrone and Oestradiol. As we age, decreasing levels of DHEA could be pivotal to the onset of decreased health. DHEA supplementation has shown an ability to return levels to those experienced in younger years and support overall health.

Dopamine

Dopamine is a catecholamine neurotransmitter in the brain made from L-Dopa. Being member of the catecholamine family, dopamine is a precursor to epinephrine (adrenaline) and norepinephrine (noradrenaline).

It can be supplied as a sympathomimetic drug (a drug which acts on the sympathetic nervous system) producing effects such as increased heart rate and blood pressure. Dopamine also inhibits the release of prolactin from the anterior lobe of the pituitary.

Dopamine plays a critical role in the way our brain controls our movements. Dopamine’s role is so critical to movement that if we do not have enough of it, we will lose the ability to execute smooth, controlled movements; low dopamine level is the cause of Parkinson’s disease. Conversely, too much Dopamine causes Schizophrenia!

Catecholamines

Catecholamines are chemical compounds (derived from tyrosine) that act as hormones or neurotransmitters. They are soluble and they circulate dissolved in blood.

The most abundant catecholamines are epinephrine (adrenaline), norepinephrine (noradrenaline) and dopamine. They are produced mainly from the adrenal medulla and the postganglionic fibres of the sympathetic nervous system. Adrenaline acts as a neurotransmitter in the central nervous system and as a hormone in the blood circulation.

Catecholamines levels in blood are associated with stress. Catecholamines cause general physiological changes that prepare the body for physical activity (e.g. exercise). Some typical effects are increases in heart rate, blood pressure, and blood glucose levels.

Cortisol

Cortisol is a steroid hormone made in the adrenal glands, which are small glands adjacent to the kidneys. Its important functions in the body include roles in the regulation of blood pressure and cardiovascular function as well as regulation of the body’s use of proteins, carbohydrates, and fats. Cortisol secretion increases in response to any stress in the body, whether physical (such as illness, trauma, surgery, or temperature extremes) or psychological. When cortisol is secreted, it causes a breakdown of muscle protein, leading to release of amino acids (the “building blocks” of protein) into the bloodstream. These amino acids are then used by the liver to synthesise glucose for energy, in a process called gluconeogenesis. This process raises the blood sugar level so the brain will have more glucose for energy. At the same time the other tissues of the body decrease their use of glucose as fuel. Cortisol also leads to the release of so-called fatty acids, an energy source from fat cells, for use by the muscles. Taken together, these energy-directing processes prepare the individual to deal with stress and ensure that the brain receives adequate energy sources.

The body possesses an elaborate feedback system for controlling cortisol secretion and regulating the amount of cortisol in the bloodstream. The pituitary gland (a small gland at the base of the brain) makes and secretes a hormone known as adrenocorticotrophin, or ACTH. Secretion of ACTH signals the adrenal glands to increase cortisol production and secretion. The pituitary, in turn, receives signals from the hypothalamus of the brain in the form of the hormone corticotropin-releasing hormone (CRH), which signals the pituitary to release ACTH. Almost immediately after a stressful event, the levels of the regulatory hormones ACTH and CRH increase, causing an immediate rise in cortisol levels. When cortisol is present in adequate (or excess) amounts, a negative feedback system operates on the pituitary gland and hypothalamus which alerts these areas to reduce the output of ACTH and CRH, respectively, in order to reduce cortisol secretion when adequate levels are present.

Measurement of Cortisol Levels
The body’s level of cortisol in the bloodstream displays what is known as a diurnal variation – that is, normal concentrations of cortisol vary throughout a 24-hour period. Cortisol levels in normal individuals are highest in the early morning at around 6-8 am and are lowest around midnight.

Normal levels of cortisol in the bloodstream range from 6-23 mcg/dl (micrograms per decilitre).

In addition to early morning, cortisol levels may be somewhat higher after meals. While the most common test is measurement of the cortisol level in the blood, some doctors measure cortisol through a saliva sample, as salivary cortisol levels have been shown to be an index of blood cortisol levels. Sometimes by-products of cortisol metabolism are also measured, such as “17-hydroxycorticosteroids”, which are inactive products of cortisol breakdown in the liver. In some cases measurement of urinary cortisol levels is of value. For this test, urine is collected over a 24-hour period and analysed.

Normal 24-hour urinary cortisol levels range from 10-100 micrograms/ 24 hours.

Anti-Cortisol
Vitamin C, 3 x 1000mg dose per day
Phosphatidylserine 800mg

Cholesterol

Cholesterol is a soft, waxy substance found among the lipids (fats) in the bloodstream and in all your body’s cells. It’s an important part of a healthy body because it’s used to form cell membranes, some hormones and is needed for other functions. But a high level of cholesterol in the blood (hypercholesterolemia) is a major risk factor for coronary heart disease, which leads to heart attack.
Cholesterol and other fats can’t dissolve in the blood. They have to be transported to and from the cells by special carriers called lipoproteins. There are several kinds, but the ones to focus on are low-density lipoprotein (LDL), high-density lipoprotein (HDL) and Lp(a).

LDL cholesterol
Low-density lipoprotein is the major cholesterol carrier in the blood. If too much LDL cholesterol circulates in the blood, it can slowly build up in the walls of the arteries feeding the heart and brain. Together with other substances it can form plaque, a thick, hard deposit that can clog those arteries. This condition is known as atherosclerosis. A clot (thrombus) that forms near this plaque can block the blood flow to part of the heart muscle and cause a heart attack. If a clot blocks the blood flow to part of the brain, a stroke results. A high level of LDL cholesterol (160 mg/dL and above) reflects an increased risk of heart disease. That’s why LDL cholesterol is called “bad” cholesterol. Lower levels of LDL cholesterol reflect a lower risk of heart disease.

HDL cholesterol
About one-third to one-fourth of blood cholesterol is carried by HDL. Medical experts think HDL tends to carry cholesterol away from the arteries and back to the liver, where it’s passed from the body. Some experts believe HDL removes excess cholesterol from plaques and thus slows their growth. HDL cholesterol is known as “good” cholesterol because a high HDL level seems to protect against heart attack. The opposite is also true: a low HDL level (less than 40 mg/dL) indicates a greater risk. A low HDL cholesterol level also may raise stroke risk.

Lp(a) cholesterol
Lp(a) is a genetic variation of plasma LDL. A high level of Lp(a) is an important risk factor for developing atherosclerosis prematurely. How an increased Lp(a) contributes to heart disease isn’t clear. The lesions in artery walls contain substances that may interact with Lp(a), leading to the buildup of fatty deposits.

Cholesterol and Diet
People get cholesterol in two ways. The body (mainly the liver) produces varying amounts, usually about 1,000 milligrams a day. Foods also can contain cholesterol. Foods from animals (especially egg yolks, meat, poultry, fish, seafood and whole-milk dairy products) contain it. Foods from plants (fruits, vegetables, grains, nuts and seeds) don’t contain cholesterol.

Typically the body makes all the cholesterol it needs, so people don’t need to consume it. Saturated fatty acids are the main culprit in raising blood cholesterol, which increases your risk of heart disease. Trans-fats also raise blood cholesterol. But dietary cholesterol also plays a part. Reports state that the everyday man consumes 337 milligrams of cholesterol a day and the everyday woman, 217 milligrams. Some of the excess dietary cholesterol is removed from the body through the liver. It is recommended that you limit your average daily cholesterol intake to less than 300 milligrams. If you have heart disease, limit your daily intake to less than 200 milligrams. Remember that by keeping your dietary intake of saturated fats low, you can significantly lower your dietary cholesterol intake. Foods high in saturated fat generally contain substantial amounts of dietary cholesterol.

How does exercise (physical activity) affect cholesterol?
Exercise increases HDL cholesterol in some people. A higher HDL cholesterol is linked with a lower risk of heart disease. Exercise can also help control weight, diabetes and high blood pressure. Exercise that uses oxygen to provide energy to large muscles (aerobic exercise) raises your heart and breathing rates. Regular moderate to intense exercise such as brisk walking, jogging and swimming also condition your heart and lungs. Physical inactivity is a major risk factor for heart disease. Even moderate-intensity activities, if done daily, help reduce your risk. Examples are walking for pleasure, gardening,, housework, and dancing.

How does tobacco smoke affect cholesterol?
Tobacco smoke is one of the six major risk factors of heart disease that you can change or treat. Smoking lowers HDL cholesterol levels.

How does alcohol affect cholesterol?
In some studies, moderate use of alcohol is linked with higher HDL cholesterol levels. However, because of other risks, the benefit isn’t great enough to recommend drinking alcohol if you don’t do so already.

Anti-Cholesterol
Simvastatin (prescription)
Niacin 3g/day
Guggalsterones
Red Yeast Rice contains Lovastatin and 3g of this rice per day has an anti-cholesterol effect.

Erythropoietin (EPO)

EPO is a glycoprotein hormone (165 amino acids in sequence) which regulates red blood cell formation; erythropoiesis. It has been found that it is produced in the liver, the brain and uterus. Erythropoietin stimulates stem cells (in the bone marrow) to increase production of erythrocytes (red blood cells).

EPO (in the form of the drug Epogen) has been extensively used as a doping drug in some sports (particularly cycling and long-distance running) because higher counts of red blood cells are beneficial for endurance due to increased oxygen transport. However, increased blood volume carries with it potential side effects, most obvious being high blood pressure.

Gamma-Amino-Butyric Acid (GABA)

GABA is a neurotransmitter. We synthesise GABA from glutamate. This was a popular supplement used by athletes to increase growth hormone and serotonin levels, it is now banned in the uk. The growth hormone helped build muscle mass, prevent muscle loss and boosted recovery. The serotonin boost aided with sleep as melatonin (hormone primarily involved with sleep) is made from serotonin.

Growth Hormones

Growth Hormone-Releasing Hormone (GHRH)
Growth hormone-releasing hormone is released from the hypothalamus and stimulates the release of growth hormone.

Growth Hormone (GH)
GH is really called somatrophin (somatropin). HGH refers to human growth hormone. Human growth hormone is a protein of 191 amino acids and is secreted by the anterior pituitary gland. Stimulators of GH release include (among others) sleep, exercise, hypoglycemia, dietary protein, and estradiol. Inhibitors of GH secretion include dietary carbohydrate and glucocorticoids.

Most of the physiologically important GH secretion occurs as several pulses or peaks of GH release each day. The level of GH during these peaks may range from 0.5-1.5 I.U or more. Peaks typically last from 10 to 30 minutes before returning to basal levels. The largest and most predictable of these GH peaks occurs about an hour after onset of sleep.

The amount and pattern of GH secretion change throughout life. Basal levels are highest in early childhood. The amplitude and frequency of peaks is greatest during the pubertal growth spurt. Healthy children and adolescents average about 7 x 2 I.U peaks per 24 hours during growth “spurts”. Adults average about 5 peaks. Basal levels and the amplitude and frequency of peaks decline throughout adult life. Several molecular forms of GH circulate in the body. Much of the growth hormone in the circulation is bound to a protein (Growth Hormone Binding Protein, GHBP) which is derived from the GH receptor.

The effects of GH on the tissues of the body can generally be described as anabolic. Like most other protein hormones, GH acts by interacting with a specific receptor on the surface of cells.

Height growth in childhood is the best known effect of GH action, and appears to be stimulated by at least two mechanisms. First, GH directly stimulates division and multiplication of chondrocytes of cartilage. These are the primary cells in the growing ends (epiphyses) of children’s long bones (arms, legs, fingers). Second, GH also stimulates production of insulin-like growth factor 1 (IGF-I).

Although height growth is the best known effect of GH, it serves many other metabolic functions as well. GH increases calcium retention, and strengthens and increases the mineralisation of bone. It increases muscle mass; particularly type 1 muscle fibre. However in presence of testosterone type 2 muscle fibres grow. GH induces growth of many different organ systems of the body, resulting in a “positive nitrogen balance”. Insulin is a very important co-factor for growth. There has been much debate about GH and insulin effects, particularly when both are present at the same time. Most recent research proves that insulin is needed along side GH to induce both growth of new cells and up-take the full spectrum of amino acids us humans require to synthesise muscle tissue. GH promotes lipolysis, which results in a great reduction of adipose tissue (body fat) and rising amounts of free fatty acids and glycerol in the blood.

Synthetic growth hormones are available, they included (but are not limited to) Nutropin (Genentech), Humatrope (Lilly), Genotropin (Pfizer), Norditropin (Novo), and Saizen (Serono). The products are nearly identical in composition, efficacy (potency), and cost ( which is very expensive), varying primarily in the formulations and delivery devices.

Insulin-like Growth Factors (IGFs)
The insulin-like growth factors (IGFs) are polypeptides with high sequence similarity to insulin. They can trigger the same cellular responses as insulin. IGF-II is thought to be a primary growth factor required for early development while IGF-I expression is seen in later life. IGF-II is essential for development and function of organs such as the brain (and nerves), liver and kidney.

IGF-I is produced by the liver and target tissues. Production is stimulated by growth hormone and retarded by undernutrition. A large fraction of circulating IGF-I is attached to IGF binding proteins (IGFBP). Its primary action is mediated by binding to specific IGF receptors present on many cell types in many tissues. The effect is the promotion of cell growth and multiplication. Almost every cell in the human body is affected by IGF-I, especially cells in muscle, cartilage, bone, liver, kidney, nerves, skin, and lungs.

IGF-I is produced throughout life. The highest rates of IGF-I production occur during the pubertal growth spurt. The lowest levels occur in infancy and old age.

IGF-I levels can be measured in the blood in 10-1000 ng/ml amounts. As levels do not fluctuate greatly throughout the day, IGF-I is used by physicians as a screening test for growth hormone deficiency and excess.

IGF-I is present in milk, especially when the cow has been treated with bovine growth hormone.

There are many other very important growth factors, which all have a role in the growth of cells. They include: Mechano Growth Factor (MGF),
Vascular Endothelial Growth Factor (VEGF), Epidermal Growth Factor (EGF), Platelet-Derived Growth Factor (PDGF), Fibroblast Growth Factors (FGFs); FGF1 (acidic-FGF, aFGF) and FGF2 (basic-FGF, bFGF) and Transforming Growth Factors (TGFs); Transforming Growth Factors-b TGFs-b), Transforming Growth Factor-a (TGF-a).

We have not listed a function for these, although some are pretty self explanatory, as we feel it is beyond the scope of this site. We will finish by saying that in terms of muscle growth, a lot of research has gone into making active synthetic forms of both IGF-I and now MGF. Long R-3 IGF-I has been made (and is resistant to liver destruction). It is quoted as being 10 times more anabolic than recombinant IGF-I (rIGF-1). MGF has been shown to be even more potent than both GH and IGF-I for increasing muscle mass! Research is now being done into using MGF for various muscle diseases.

Glucocorticoids

Glucocorticoids are steroid-like substance capable of influencing metabolism, regulating the immune system and exerting an anti-inflammatory effect. The two most important to mention are Cortisol and Glucagon. Cortisol (hydrocortisone) is the most potent of the naturally occurring glucocorticoids and is very catabolic to muscle. Glucagon breaks muscle stored glycogen into glucose (opposite effect to insulin).

People wishing to build muscle must make effort to control cortisol levels. Overtraining is a sure way of increasing cortisol levels so the first way to suppress cortisol is to not overtrain! See the cortisol section for more info.

Gut Hormones and Appetite

Over two dozen hormones have been identified in various parts of the gastrointestinal system. All of them are peptides and many of them are also found in other tissues, especially the brain.

The following eight hormones are the ones most people associate with digestion and appetite:

Gastrin
Gastrin is a mixture of several peptides. It is secreted by cells in the stomach and duodenum. Gastrin stimulates the exocrine cells of the stomach to secrete gastric juice; a mixture of hydrochloric acid and pepsin.

Secretin
Secretin is secreted by cells in the duodenum when they are exposed to the acidic contents of the emptying stomach. It stimulates the exocrine portion of the pancreas to secrete bicarbonate into the pancreatic fluid (thus neutralising the acidity of the intestinal contents).

Cholecystokinin (CCK)
CCK is also a mixture of peptides which are secreted by cells in the duodenum when they are exposed to food. It acts on the gall bladder, stimulating it to contract and force its contents of bile into the intestine. CCK also acts on neurons leading back to the medulla oblongata which give a satiety signal: in other words this hormone makes you feel full after eating.

Somatostatin
This hormone is covered in its own section but in relation to gut hormones and appetite it is important to mention as it inhibits the release of gastrin. It acts on the duodenum where it inhibits the release of secretin and cholecystokinin . Also, acts on the pancreas where it inhibits the release of glucagon.

Taken together, all of these actions lead to a reduction in the rate at which nutrients are absorbed from the contents of the intestine. Somatostatin is also secreted by the hypothalamus and the pancreas.

Ghrelin
Ghrelin is the hunger hormone. It’s made in the stomach, and it acts on the hypothalamus to stimulate feeding; i.e it generates a hunger feeling. Ghrelin doesn’t cause obesity, but scientists think taming it might help us control over-eating eating habits . It is secreted by endocrine cells in the stomach. This action counteracts the inhibition of feeding by leptin and PYY3-36 .

Neuropeptide Y (NPY)
Neuropeptide Y (which is also secreted by neurons in the hypothalamus) is a potent feeding stimulant and causes increased storage of ingested food as fat. Neuropeptide Y also blocks the transmission of pain signals to the brain.

PYY3-36
Peptide YY3-36 contains 34 amino acids, many of them in the same positions as those in neuropeptide Y. However, the action of PYY3-36 is just the reverse of that of NPY, being a potent feeding inhibitor. It is released by cells in the intestine after meals. The amount secreted increases with the number of calories that were ingested. PYY3-36 acts on the hypothalamus to suppress appetite. It also acts on the pancreas to increase its exocrine secretion of digestive juices and the gall bladder to stimulate the release of bile. The appetite suppression mediated by PYY3-36 works more slowly than that of cholecystokinin and more rapidly than that of leptin.

Leptin
Leptin is manufactured in fat cells (adipose tissue), and the level of circulating leptin is directly proportional to the total amount of fat in the body. Leptin acts on receptors in the hypothalamus of the brain where it counteracts the effects of neuropeptide Y: the result being inhibition of food intake.
This inhibition is long-term, in contrast to the rapid inhibition of eating by cholecystokinin (CCK) and the slower suppression of hunger between meals mediated by PPY3-36

The absence of this functional hormone (or its receptor) leads to uncontrolled food intake and results in obesity. Leptin also acts on hypothalamic neurons responsible for stimulating the secretion of gonadotropin-releasing hormone (GnRH). You may be interested to know that women who are very thin from limited food intake or intense physical training may cease to menstruate because of their lack of leptin-secreting fat cells.

In addition to its effect on the hypothalamus, leptin acts directly on the cells of the liver and skeletal muscle where it stimulates the oxidation of fatty acids in the mitochondria. This reduces the storage of fat in those tissues (but not in adipose tissue).

Insulin

Insulin is synthesised in humans and other mammals within the beta cells (B-cells) of the islets of Langerhans in the pancreas. Within the islets of Langerhans, beta cells constitute 60-80% of all the cells.

Insulin is built from 51 amino acids and is one of the smallest proteins known. Beef (bovine) insulin differs from human insulin in two amino acid residues, and pork insulin in one residue. Fish insulin is also close enough to human insulin to be effective. Insulin is produced as a prohormone molecule (pro-insulin), that is later transformed into the active hormone.

Insulin is the primary effector in carbohydrate homeostasis (blood sugar regulation); it converts glucose into glycogen. However, insulin also takes part in the metabolism of fat (triglycerides) and proteins. It has very anabolic properties; it is quoted as being the most anabolic hormone known for a human. Glucagon has the opposite effect to insulin; it turns glycogen into glucose.

Two types of tissues are most strongly influenced by insulin: muscle cells (myocytes) and fat cells (adipocytes). Myocytes are important because of their central role in movement, breathing, circulation, etc, and adipocytes because they accumulate excess calories against future needs (give you a “fuel tank”). Together, they account for about 2/3 of all cells in a typical human body.

Insulin and Diabetes Mellitus
Insulin is used medically in some forms of diabetes mellitus. Patients with Type 1 diabetes mellitus depend on exogenous insulin (injected subcutaneously) for their survival because of an absolute deficiency of the hormone; patients with Type 2 diabetes mellitus have either relatively low insulin production or insulin resistance, and occasionally require insulin administration if other medications are inadequate in controlling blood glucose levels.

Summary of the Actions of Insulin on Cells
1) Increased glycogen synthesis: insulin forces storage of glucose in liver (and muscle) cells in the form of glycogen. Lowered levels of insulin cause liver cells to convert glycogen to glucose and dump it into the blood; hence “homeostasis” (regulation of blood sugar).

2) Increased fatty acid synthesis: insulin forces fat cells to take in glucose which is converted to fatty acids. Lack of insulin causes the reverse

3) Increased esterification of fatty acids: forces adipose tissue to make fats (ie, triglycerides) from fatty acid esters. Lack of insulin causes the reverse

4) Decreased proteinolysis: forces reduction of protein degradation. Lack of insulin increases protein degradation. So, one can appreciate how important insulin is if attempting to build muscle or conserve muscle tissue.

5) Decreased lipolysis: forces reduction in conversion of fat cell lipid stores into blood fatty acids. Lack of insulin causes the reverse.

6) Decreased gluconeogenesis: decreases production of glucose from various substrates in liver. Lack of insulin causes glucose production from assorted substrates in the liver and elsewhere.

7) Increased amino acid uptake: forces cells to absorb circulating amino acids. Lack of insulin inhibits absorption. Again, one can appreciate how important insulin is if attempting to build muscle or conserve muscle tissue.

8) Increased potassium uptake: forces cells to absorb serum potassium. Lack of insulin inhibits absorption.

9) Arterial muscle tone: forces arterial wall muscle to relax increasing blood flow, especially in “micro arteries”. Lack of insulin reduces flow by allowing these arterial wall muscles to contract.

Genetics
Both Type 1 and Type 2 diabetes are at least partly inherited. Type 1 diabetes appears to be triggered by infection, stress, or environmental factors (e.g. exposure to a causative agent). There is a genetic element in the susceptibility of individuals to some of these triggers which has been traced to particular HLA genotypes (i.e. genetic ‘self’ identifiers used by the immune system). However, even in those who have inherited the susceptibility, Type 1 diabetes mellitus seems to require an environmental trigger.

There is an even stronger inheritance pattern for Type 2 diabetes; those with Type 2 ancestors or relatives have very much higher chances of developing Type 2. It is also often connected to obesity, which is found in approximately 85% of (North American) patients diagnosed with that form of the disease, so inheriting a tendency toward obesity seems also to contribute. Age is also thought to be a contributing factor, as most Type 2 patients in the past were older. The exact reasons for these connections are unknown.

Regulatory Action on Blood Glucose
Human blood glucose levels normally remain within a narrow range. In most humans this varies from person to person from about 70 mg/dl to 110 mg/dl. After eating, especially if eating high glycemic index foods, your blood sugar level increases. Conversely, prolonged periods of not eating cause stored glucose (glycogen) to be released into bloodstream. This homeostatic process is the result of many factors, but hormone regulation is the most important.

There are two groups of hormones affecting blood glucose levels:
1) Hyperglycemic hormones (such as glucagon, growth hormone, and adrenaline), which increase blood glucose level

2) A hypoglycemic hormone, insulin, which as you’ll have learned by now, decreases blood glucose level.

It is far less dangerous to have too much glucose in the blood than too little. Mechanisms which restore too low blood glucose (hypoglycemia) must be quick and effective because of serious consequences of insufficient glucose.

Beta cells in the islets of Langerhans are sensitive to variations in blood glucose levels because of the presence of glucokinase, which responds to glucose concentrations. If that level increases, more insulin from beta cell stores is released into the blood, and beta cell insulin production increases. When the glucose level comes down to its normal level, insulin release slows or stops. And, before the level of glucose drops dangerously low, hyperglycemic hormones come into play, forcing release of glucose into the blood from cellular stores.

The Brain and Hypoglycemia
Though other cells can use other fuels for a while (most prominently fatty acids), neurons are dependent on glucose as a source of energy in the non-starving human. They do not require insulin to absorb glucose, unlike muscle and adipose tissue, and they have very small internal stores of glycogen. Thus, a sufficiently low glucose level first and most dramatically manifests itself in impaired functioning of the central nervous system; dizziness, speech problems, even loss of consciousness, are common. This phenomenon is known as hypoglycemia or, in cases producing unconsciousness, hypoglycemic coma (insulin shock).

Causes of hypoglycemia include:
1) oral hypoglycemic agents (eg, sulfonylureas, or similar drugs) which increase insulin release from beta cells in response to a particular blood glucose level)

2) external insulin (usually injected subcutaneously).

Considerations when using Insulin:
There are several difficulties with the use of insulin, both as a clinical treatment for diabetes and for those choosing to use it to increase mass/performance (which is more common than perhaps people realise):

1) method of administration
2) selecting the ‘right’ dose and timing
3) selecting an appropriate insulin preparation (typically on ‘speed of onset and duration of action’ grounds)
4) adjusting dosage and timing to fit food amounts and types
5) adjusting dosage and timing to fit exercise undertaken
6) adjusting dosage, type, and timing to fit other conditions as for instance the increased stress of illness

Diabetics (and those choosing to use it) give themselves insulin, usually via subcutaneously hypodermic injection. This is both non-physiologic (the pancreas releases insulin (and C-peptide) gradually into the portal vein instead of subcutaneously) and simply a nuisance for patients to inject themselves once or several times a day. Also, it is dangerous in case of mistake (especially too much insulin)

Unlike many medicines, insulin cannot (yet) be taken orally. It is treated in the gastrointestinal tract precisely as any other protein; that is, reduced to its amino acid components ( so all insulin activity is lost). There are research efforts underway to develop methods of protecting insulin from the digestive tract so that it can be taken orally; Inhaled insulin is under active investigation as are several other techniques.

Insulin Types
Medical preparations of insulin (Eli Lilly and Novo Nordisk or from any other) are never just ‘insulin in water’. Clinical insulins are specially prepared mixtures of insulin plus other substances. These delay absorption of the insulin, adjust the pH of the solution to reduce reactions at the injection site, and so on. Some recent insulins are not even precisely insulin, but so called insulin analogues. The insulin molecule in an insulin analogue is slightly modified so that they are: 1) absorbed rapidly enough to mimic real beta cell insulin (Lilly’s ‘lispro’ and Novo Nordisk’s ‘aspart’). 2) steadily absorbed after injection, instead of having a ‘peak’ followed by a more or less rapid decline in insulin action all while retaining insulin action in the human body.

The management of choosing insulin type and dosage/timing should be done by an experienced medical professional.

Exapmles of Insulins
The following semi-comprehensive list gives examples of the different types of insulin availiable.

Product Manufacturer Form

Rapid acting (onset less than 15 minutes)
Humalog (insulin lispro) Lilly Human
Humalog Cartridge (3 ml and 1.5 ml) Lilly Human
Humalog Prefilled Pen (3 ml, packets of 5) Lilly Human
NovoLog PenFill (insulin aspart) (3 ml) Novo Nordisk Human
NovoLog (insulin aspart) Novo Nordisk Human

Short acting (onset 0.5–2 hours)
Humulin R (regular) Lilly Human
Iletin II Regular Lilly Pork
Novolin R (regular) Novo Nordisk Human
Novolin R PenFill (3 ml) Novo Nordisk Human
Novolin R (regular) Novo Nordisk Human

Intermediate acting (onset 2–4 hours)
Humulin L (lente) Lilly Human
Humulin N (NPH) Lilly Human
Humulin N Prefilled Pen (3 ml, 5 pack) Lilly Human
Iletin II NPH Lilly Pork
Novolin L (lente) Novo Nordisk Human
Novolin N (NPH) Novo Nordisk Human
Novolin N PenFill (3 ml) Novo Nordisk Human
Novolin N (NPH) Novo Nordisk Human

Long acting
Humulin U (ultralente) (onset 4–6 hours) Lilly Human
Lantus (insulin glargine) (onset 1.1 hours) Aventis Human

Mixtures
Humulin 50/50 Lilly Human
Humulin 70/30 Lilly Human
Humulin 70/30 Prefilled Pen Lilly Human
Humalog Mix 75/25 Lilly Human
Humalog Mix 75/25 Prefilled Pen Lilly Human
Novolin 70/30 Novo Nordisk Human
Novolin 70/30 PenFill Novo Nordisk Human
NovoLog Mix 70/30 Novo Nordisk Human
Novolin 70/30 Novo Nordisk Human

Interleukins

Interleukins are a group of cytokines that are expressed by white blood cells (leukocytes, hence the -leukin) as a means of communication (inter-) between cells. The function of the immune system depends largely on interleukins. Deficiencies of a number of them can lead to autoimmune diseases or immune deficiency.

Here is list of some interleukins (IL-) and their function so that you get an idea of their “communication” properties in the immune system:

IL-2: secreted by T cells, stimulates growth and differentiation of T cell response. Can be used in immunotherapy to treat cancer.
IL-3: secreted by T cells, stimulates bone marrow stem cells.
IL-4: involved in proliferation of B cells, and the development of T cells and mast cells. Important role in allergic responses.

Immunoglobulins

Firstly, an antibody is a protein complex (glycoprotein) used by the immune system to identify and neutralise foreign objects (pathogens) like bacteria and viruses; immunoglobulins are a type antibody.

Immunoglobulins are grouped into five classes: IgG, IgA, IgM, IgD, and IgE. Differences in the chemical structure of the immunoglobulin determine its function and which of the following five classes it belongs to. Other immune cells partner with antibodies to eliminate pathogens depending on which IgG, IgA, IgM, IgD, and IgE constant binding domain receptors it can express on its surface.

IgG is an immunoglobulin that is present in normal blood and is the most numerous. This immunoglobulin can bind to many kinds of pathogens, for example viruses, bacteria, and fungi to fight against toxins. There are 4 subclasses: IgG1 (66%), IgG2 (23%), IgG3 (7%) and IgG4 (4%)

IgA represent about 15 to 20% of immunoglobulins in the blood although it is primarily secreted across the mucosal tract into the stomach and intestines. This immunoglobulin helps to fight against pathogens that contact the body surface, ingested, or inhaled. It exists in two forms, IgA1 and IgA2.

IgM is an immunoglobulin that can detect whether a person has ABO blood type. It is also important in fighting bacteria.

IgD immunoglobulins make up about 1% in the plasma membranes in B-lymphocytes. These immunoglobulins are involved in the development of plasma and memory cells that are in the B-lymphocytes.

IgE is an immunoglobulin that can be found on the surface of the plasma membrane of “basophils” and “mast cells” of connective tissue. IgE can also be found in involved with diseases such as hypersensitivity and also in the defence of parasites such as worms.

Luteinizing Hormone

In both sexes, LH stimulates secretion of sex steroids from the gonads. In the testes, LH binds to receptors on Leydig cells, stimulating synthesis and secretion of testosterone. The cells in the ovary respond to LH stimulation by secretion of testosterone, which is converted into estrogen by adjacent granulosa cells.

In females, ovulation of mature follicles on the ovary is induced by a large burst of LH secretion known as the preovulatory LH surge. Residual cells within ovulated follicles proliferate to form corpora lutea, which secrete the steroid hormones progesterone and estradiol. Progesterone is necessary for maintenance of pregnancy, and, in most mammals, LH is required for continued development and function of corpora lutea. The name luteinizing hormone derives from this effect of inducing luteinization of ovarian follicles.

Follicle-Stimulating Hormone

As its name implies, FSH stimulates the maturation of ovarian follicles. Administration of FSH to humans and animals induces “superovulation”, or development of more than the usual number of mature follicles and hence, an increased number of mature gametes (sex cells).

FSH is also critical for sperm production. It supports the function of Sertoli cells, which in turn support many aspects of sperm cell maturation.

Control of Gonadotropin Secretion
The principle regulator of LH and FSH secretion is gonadotropin-releasing hormone or GnRH (also known as LH-releasing hormone). GnRH stimultes secretion of LH, which in turn stimulates gonadal secretion of the sex steroids testosterone, estrogen and progesterone. In a classical negative feedback loop, sex steroids inhibit secretion of GnRH and also appear to have direct negative effects on gonadotrophs (cells in the anterior pituitary).

This regulatory loop leads to pulsatile secretion of LH and, to a much lesser extent, FSH. The number of pulses of GnRH and LH varies from a few per day to one or more per hour. In females, pulse frequency is clearly related to stage of the cycle.

Numerous hormones influence GnRH secretion, and positive and negative control over GnRH and gonadotropin secretion is complex. For example, the gonads secrete at least two additional hormones (inhibin and activin) which selectively inhibit and activate FSH secretion from the pituitary, but we need not go into that here.

Leukotrienes

Leukotrienes play an important role in inflammation. They are synthesized, via lipoxygenase, in leukocyte cells (and macrophages) from arachidonate acid.

Blocking leukotriene receptors can play a positive role in the management of asthma.

Melatonin

Melatonin (5-methoxy-N-acetyltryptamine) is a hormone produced by pinealocytes in the pineal gland, located in the centre of the brain. Melatonin is made from serotonin. Melatonin helps regulate sleep-wake patterns. Normally, production of melatonin by the pineal gland is stimulated by darkness and inhibited by light.

In recent times, melatonin has become available as a drug and a dietary supplement. It appears to have some use against insomnia and jet lag. It has been studied for the treatment of cancer, immune disorders, cardiovascular diseases, depression, seasonal affective disorder, and sexual dysfunction; no apparent benefit in these has been found.

Evidence shows that melatonin can give you wild and vivid dreams!

Mineralocorticoid

Mineralocorticoids is a class of steroids characterised by their similarity to aldosterone and their influence on salt and water metabolism.

The only endogenous mineralocorticoid is aldosterone, although a number of hormones (mainly progesterone) have mineralocorticoid function. An example of synthetic mineralocorticoids is fludrocortisone. An important mineralocorticoid inhibitor is spironolactone.

Oestrogen (estrogen)

oestrogen is labelled the female hormone, just as testosterone is labelled the male hormone. Just like testosterone, oestrogen is common to members of both sex.

Males who have high oestrogen levels will most likely suffer from female characteristics, including breasts (gynecomastia) and fat deposits around stomach, hips, buttocks and thighs. It is still useful (but in low amounts) to males as it plays a role in the production of IGF-1 in adipose (fat) cells. Fact is, the fatter the man is, the more oestrogen he produces and so the more woman he becomes!

As well as giving women their feminine characteristics, it plays a vital role in many of the female biochemical processes. Oestrogen is involved in the lactation process, regulating bone density in a foetus and it also protects female foetuses from the effects of androgens (like testosterone) in the mother’s system.

Oestrogen is the name given to a family of ovarian hormones which all have similar characteristics. There are three principle forms of oestrogen found in the human body oestrone (estrone), oestradiol (estradiol) and oestriol (estriol), also known as E1, E2 and E3 respectively. Oestradiol (E2) is the primary oestrogen produced by the ovaries. Oestrone (E1) is formed from oestradiol. It is a weak oestrogen and is the most abundant oestrogen found in the body after menopause. Oestriol (E3) is produced in large amounts during pregnancy and is a breakdown product of oestradiol. oestriol is also a weak oestrogen and may have anti-cancer effects. Before menopause oestradiol is the predominant oestrogen. After menopause oestradiol levels drop more than oestrone so that now oestrone is the predominant oestrogen.

During the female menstruation cycle, the production of oestrogen is controlled by the hormone LH (Leutenising Hormone) both indirectly and directly. The “Yellow Body” (corpus luteum) is directly stimulated by LH to produce oestrogen, whereas before ovulation, the granulosa cells of the follicle are stimulated to produce oestrogen via the aromatase enzyme.

As with progesterone, oestrogen is produced by the placenta throughout a pregnancy and the levels increase steadily until birth. Each hormone plays a vital and complex role during a pregnancy and many of them interact with each other to stimulate various parts of the process. One role of oestrogen during pregnancy is to regulate the production of progesterone over the full term.

Pheromones

The definition of a pheromone is; “A chemical produced by an organism that signals its presence to other members of the same species”. Pheromones are detected by an organ called Vomeronasal organ (VNO) which is a small sac on either side of the nasal septum, containing receptor cells that pick up chemical signals (pheromones) from other organisms of the same species.

Pregnenolone

Pregnenolone is a hormone manufactured from cholesterol in the cells of many organs. It is a precursor to DHEA from which testosterone, estrone and Oestradiol are made . Numerous studies show the benefits of supplementing with pregnenolone. Ongoing human trials are showing benefit to those suffering from decreases in cognitive function memory loss, joint pain and skin ailments. Recent reports indicate the value of pregnenolone for menstrual irregularities and menopause. Production of pregnenolone decreases with age.

Progesterone

Progesterone means pro (supporting) gesterone (gestation or pregnancy). Progesterone is the other hormone your ovaries make, other than oestrogen, and its main function is to support pregnancy. Progestogens can be either natural or synthetic. The natural form when taken by mouth is rapidly broken down by the liver this is why in 1934 a synthetic form was developed. There are now more than 10 synthetic forms of progestogen. A new form called micronized (broken down into tiny particles) progesterone has recently become available, the micronized progesterone resists breakdown.

Progestogens have been used for years in infertility treatment and to replace the natural progesterone in women with premature ovarian failure. Progestogens are used to treat abnormal uterine bleeding and for contraception in birth control pills and in Depo-Provera. They are also used to prevent the negative effects of oestrogen on the uterus when used for hormone replacement therapy and they are used for the treatment of PMS.

There are two controversial topics you may have heard of. First is the use of natural versus synthetic progestogens in hormone replacement therapy. Second is the use of progesterone in the treatment of PMS (premenstrual syndrome), especially the recent popularity of the natural progesterone creams.

Hormone replacement therapy (HRT) is recommended for most women after menopause. HRT consists of the hormone oestrogen and, if your uterus has not been removed, progesterone. It’s commonly known that oestrogen supplementation alone can cause endometrial (uterine) cancer. When a progestogen is added, the chance of uterine cancer is reduced below the base line level. One of oestrogen’s many benefits is it’s ability to reduce the risk of heart disease. One of the ways oestrogen does this is by increasing HDL or (good cholesterol). Synthetic progestogens tend to reduce this benefit. Natural micronized progesterone does not appear to reduce estrogens positive effect on cholesterol. Therefore this is one case where the natural form of progesterone may be better for you.

PMS is a major problem for millions of women around the world. Until recently there has been no effective treatment. One of the theories about the causes of PMS is that there is an imbalance between oestrogen and progesterone. This theory has led to the treatment of PMS with progesterone. There have been over 20 scientific studies of the treatment of PMS with progesterone, the vast majority of which have found progesterone to be ineffective. There are a few small studies that have shown some relief of some symptoms of PMS with progesterone. Progesterone, especially in expensive cream form is marketed as a cure for obesity, depression, foggy thinking, osteoporosis and wrinkles to name a few. These claims, made by some manufactures are unsubstantiated.

Side Effects
Progestogens should not be used if you have had blood clots in the legs (thrombophlebitis) or liver disease. Use in pregnancy requires careful physician surveillance. Progesterone can also cause bloating, breast tenderness, weight gain, headache, moodiness and irregular vaginal bleeding. Progestegens can cause some medical conditions to worsen examples are asthma, heart failure, epilepsy and migraine headache. Natural progesterone tends to have fewer side effects.

Anti-Progestin
Tamoxifen 20mg/day
Formestane is also an anti-progestin, it decreases oestrogen and increases IGF-1 by 26%

Prolactin

Prolactin is produced from the anterior pituitary gland, it’s found in the serum of normal females and males. Prolactin’s principal physiological action is to initiate and sustain lactation (production of breast milk). Prolactin secretion is pulsatile and shows daily variation, with the serum concentration increasing during sleep and is at its lowest approx. 3 hours after waking. The secretion of prolactin is increased by stress and is dependent upon a women’s oestrogen status.

The analysis of prolactin can be used for the diagnosis and treatment of disorders of the anterior pituitary gland or the hypothalamus.

Prolactin Control
Bromocriptine 2.5mg/day is a way of supressing prolactin secretion.

Prostaglandins

Our bodies regulate many cellular events through mediators or substances that act with, or for, other chemicals to create a specific environment. Of these, the prostaglandins are primary factors in determining the amount of muscle mass you are able to build and the percentage of fat you burn daily as heat or simple calorie expenditure.

Prostaglandins are found in virtually all tissues and organs and are derived from lipids. They act upon platelet, endothelium, uterine and mast cells among others. They are formed by the action of cyclooxygenase; the cyclooxygenase pathway produces thromboxane, prostacyclin and prostaglandin D, E and F ( and leukotriene).

There are currently nine known receptors of prostaglandins on various cell types. Prostaglandins thus act on a variety of cells such as vascular smooth muscle cells causing constriction or dilation, on platelets causing aggregation or disaggregation and on spinal neurons causing pain. Prostaglandins act principally on subfamily of G-Protein Coupled Receptors (GPCR). Most of these GPCRs are located at the periphery of target cells at the plasma membrane, however, a few exist within the cell at the nuclear envelope. Prostaglandins have a wide variety of actions but most cause muscular constriction and mediate inflammation. Other effects can be calcium movement, hormone regulation and cell growth control; which is an important property to those wishing to build muscle.

There are three types of prostaglandins defined as series:

Prostaglandin Series 1 (PGE-1):
Anabolic in action with the ability to mediate many the activities of growth promoting hormones. They also protect the body against the negative effects of the PGE-2 series.

Prostaglandin Series 2 (PGE-2):
With the exception of the highly anabolic PGF-2, the PGE-2 series induces negative and anti-growth effects. Some of the more obvious side effects of excess or unchecked production are sticky platelets, excessive inflammation, water retention, decreased rate of recovery and suppressed immune function.

Prostaglandin Series 3 (PGE-3):
The PGE-3 series has the dubious job of inhibiting the activities of PGE-2 while aiding the activities of PGE-1.

Prostaglandins are potent but have a short half-life before being inactivated and excreted. Synthetic prostaglandins are used for a number of reasons: to induce childbirth (PGE2 or PGF2, with mifepristone), to close a patent ductus arteriosus in newborns, to prevent and treat peptic ulcers (PGE) and as a vasodilator in severe Raynaud’s phenomenon or ischemia of a limb

Non-Steroidal Anti-Inflammatory Drugs (NSAID) inhibit cyclooxygenase and reduce prostaglandin synthesis. Aspirin-like like drugs could inhibit the synthesis of prostaglandins.

Serotonin

Serotonin (5-hydroxy-tryptamine, 5-HT or 5-HTP) is a monoamine neurotransmitter synthesised in the central nervous system. Serotonin is believed to play an important part of the biochemistry of depression, bipolar disorder, sleep and anxiety. It is also believed to be influential on sexuality. Serotonin is found extensively in the human gut, as well as in the blood stream.

Research has shown that some people who take 5-HTP noticed an improvement in their mood, reduction in anxiety, decrease in appetite, and felt they were able to sleep better. This is explainable due to the fact that melatonin is manufactured from serotonin. However, care must be taken in any attempt to increase serotonin levels, as a dangerous condition known as serotonin syndrome may result. The popular supplement GABA (now banned in uk) was taken to stimulate an increase in serotonin level (and growth hormone level); if taken before bed people reported an improved sleep (again due to melatonin production) and recovery (attributed to increased growth hormone levels).

Symptoms of low levels of serotonin include depression, obesity, carbohydrate craving, bulimia, insomnia, migraine headaches, tension headaches, chronic daily headaches and premenstrual syndrome.

Somatostatin

Somatostatin is a mixture of two peptides, one built of 14 amino acids, the other of 28. Somatostatin is secreted by the hypothalamus and also delta cells of the stomach, intestine and pancreas. It binds to somatostatin receptors.

All actions of somatostatin are inhibitory; it inhibits the release of growth hormone (GH) and thyroid stimulating hormone (TSH). Somatostatin also suppresses the release of gastrointestinal hormones; gastrin, cholecytokinin (CCK), secretin, motilin, vasoactive intestinal peptide (VIP), gastric inhibitory polypeptide (GIP) and enteroglucagon (GIP)

Other inhibitory actions include: inhibiting the release of insulin, inhibiting the release of glucagon, inhibiting the release of glucagon

Somatostatin also prolongs gastric emptying, gall bladder contraction and intestinal motility

Somatostatin Control
3g Arginine is reported to inhibit somatostatin release

Sex Hormone Binding Globulin (SHBG)

Sex hormone-binding globulin (SHBG) is a glycoprotein synthesised by the liver. Circulating androgen and oestrogen concentrations influence SHBG synthesis. Elevated testosterone, for example, causes SHBG synthesis to decrease, whereas high oestrogen stimulates SHBG production. The regulation of SHBG synthesis, combined with SHBG’s higher affinity for testosterone, impacts bioavailable testosterone levels. What this basically means is that given the choice, SHBG will bind to testosterone over oestrogen so for those wanting to keep free testosterone levels high and build muscle, make sure your oestrogen production isn’t high so that your SHBG synthesis is low. Testosterone is converted by aromatase enzyme to oestrogen, so obviously blocking or lowering this conversion rate is a sure way to prevent increased SHBG synthesis and preventing increased oestrogen levels.

Male & Female Physiological Action
Binds up to 98 percent of the steroid hormones in the blood including testosterone, DHT and androstenediol with particularly high affinity, and oestradiol and estrone with slightly lower affinity

Regulation & Secretion
Male and female children have similar SHBG concentrations until the onset of puberty, when SHBG levels begin decreasing more rapidly in males than in females.

Levels are lower in men than in women, due to the higher ratio of oestrogens to androgens in women.

Levels are especially elevated during late pregnancy and in women taking oral contraceptives.

SHBG Control
Eurycoma Longifolia Jack (long Jack), Wild oat extract (Avena Sative), Muira Puama, Copper Tartrate, Magnesaium Aspartate, Zinc Aspartate and Vitamin B-6.

Sodium-Potassium Pump

Every single cell in our bodies must constantly maintain certain ratios of sodium and potassium in order to remain alive and healthy. This balance (homeostasis) is regulated by the Sodium (Na)-Potassium (K) Pump.

The Na-K-Pump is an essential life sustaining biochemical pathway that actually “pumps” sodium and potassium in and out of each cell of the body 24 hours per day. This is crucial to maintaining important biochemical homeostasis and intercellular integrity. Many aspects of the process involving the absorption of ATP substrates and growth nutrients are mediated by this cellular pump.

The regulation of this “Pump” is provided by an enzyme called Sodium-Potassium-Adenosine Triphosphatase (Na-K-ATPase). Na-K-ATPase is activated when the body can make enough of the correlating prostaglandins through a critical intermediary Essential Fatty Acid (EFA); GLA Gamma-linolenic acid.

Testosterone

Testosterone is a hormone naturally produced by the body’s endocrine system and is something we all have. Testosterone has two different effects on the body: anabolic effects which promote growth and muscle building, and androgenic effects which develop the male sex organs and secondary sex characteristics such as deepening of the voice and growth of facial hair (virility). The amount of testosterone we produce daily depends upon a lot of things, including gender, time of day, age, menstrual cycle, menopause, stress, and medications. In men, testosterone is produced in the testes in a daily cycle (7-11mg/day). In women, ovaries and the adrenal glands produce testosterone (approx. 0.25 mg/day). For both, levels decline with age. Exactly how testosterone works is not well understood. It’s strange that something so central to our sex lives would be so little understood, but like much of life, research on testosterone is pretty skewed by cultural beliefs about masculinity and femininity. Studies suggest that testosterone directly affects muscle development (discussed in more depth shortly), fat levels, bone mass, many different parts of the brain, moods, depression, energy levels, ability to have orgasms, and ability to sleep.

Low levels of testosterone (hypogonadism) can cause symptoms of fatigue, malaise (ill feeling), loss of sex drive, and loss of muscle tissue. These symptoms can often be treated with synthetic testosterone. Anabolic steroids are compounds related to testosterone. Using synthetic testosterone or anabolic steroids may help people with low testosterone and HIV. Studies have found that testosterone can get very low in men and women with HIV/AIDS. People with HIV will benefit from exogenous (artificially added) testosterone, as it will prevent the rapid weight loss associated with HIV and they may even gain weight, especially muscle mass. This is because testosterone, as well as being anabolic and androgenic, is anti-catabolic (specifically an anti-glucocorticoid). We will mention HIV frequently here as the simple fact is, it concerns all (not just those who are sexually active) so we should all have an open minded and mature attitude to the subject. Also, there is a lot of research going on which is looking into the use of anabolic androgenic steroids (AAS) to help treat this life threatening disease. Weight loss in people with HIV and AIDS is a serious problem, even with “super-combo” therapy. Much of AIDS weight loss is a specific shortage of muscle, and in women, fat as well. With low T-cells, the body often burns up muscle instead of the usual fat and carbohydrates. This is why some PWAs (People With Aids) get skinny legs and bulging stomachs without losing weight.

Muscles need protein. Hormones like testosterone, IGF (insulin-like growth factor) and HGH (human growth hormone) help proteins find their way to muscles and stay there. They also help maintain muscle once it has been made, and help the body burn fat instead of muscle. If it wasn’t for these hormones, protein from food would not be used to make muscles, and existing muscles would get quickly burned up. Studies of low testosterone in HIV-negative people show that protein fails to build muscle, and old muscle is broken down by the body to fuel itself. Simply concluded, low testosterone levels lead to muscle loss!

Testosterone is converted to oestrogen by the action of aromatase enzyme and reduced to DHT (dihydrotestosterone) by 5-alpha-reductase enzyme. DHT is approx. 4 times more androgenic than testosterone itself. People, (especially bodybuilders) wishing to prevent conversion to oestrogen have to take anti-oestrogens. However, remember you don’t want to cut out oestrogen completely, just monitor it and keep it low as it plays a role in the production of growth hormone and IGF-1. DHT is said to be the main culprit for the many unwanted side effects of testosterone, this may be true to a degree but the fact is all anabolic androgenic steroids exert an effect on the androgen receptor. The 5-alpha-reductase enzyme is found in high amounts in tissues including the prostate, skin, scalp and liver. So, one can understand now that because of the increased potency localised in these tissues, side effects like acne due to increased sebaceous gland activity and accelerated male pattern baldness due to activity of the androgen receptors in the scalp, become possible.

Free & Bound Testosterone
A very small amount (approx. 2% in men and less than 1% in women) of testosterone actually exists as free (or unbound) testosterone. There rest is found bound to both SHBG (approx. 45%) and albumin (approx. 53%). Obviously the more free testosterone there is the greater the anabolic androgenic effect. By altering the testosterone molecule you can alter the affinity for binding to SHBG and albumin. This is why some steroids can exert a more anabolic androgenic effect than others on a milligram to milligram basis, as there will be more free testosterone available to bind to the androgen receptor as it doesn’t bind well to SHBG or albumin. Another method to increase free testosterone is to administer a steroid (like proviron) that actually likes binding to SHBG so that once you administer another testosterone (this is called stacking), most of the SHBG is “soaked-up” and so free androgen levels increase! These binding proteins do have a purpose; they protect testosterone from rapid metabolism and play a vital role in androgen transport.

Testosterone and muscle growth:
Testosterone effects those cells which carry androgen receptors, these include skeletal muscle cells, skin, scalp, kidney, bone, prostate and cells that make up the central nervous system (CNS). Testosterone makes its way into the cell (cytosol) and binds with the androgen receptor forming a “receptor-complex”. This receptor-complex migrates to the cell nucleus to bind to a specific section of DNA, this binding is called the “hormone-response-element” (HRE). The HRE activates the process of “transcription”. Transcription happens at a specific gene sequence, for example, when testosterone effects skeletal muscle, the HRE activates the transcription of genes which code for the production (translation) of the contractile proteins, actin and myosin. Once the message to produce these proteins has been delivered, the receptor-complex disassociates. Note that both are free to do this process again and the free testosterone may migrate to other cells and interact with them. This whole process doesn’t happen instantly, in fact it is quite a slow process which takes hours.

Another two properties worth mentioning in relation to muscle growth is that, firstly, testosterone has a marked effect on the release of IGF-1 (and also causes an increase in the number of IGF-1 receptor sites). Secondly, testosterone is also reported to enhance the the production of creatine in skeletal muscle.

What are anabolic steroids?
Anabolic steroids are synthetic compounds that resemble the natural hormone testosterone. Makers of anabolic steroids change the testosterone molecule slightly to change the balance of androgenic and anabolic effects, which can allow these drugs to build muscle with fewer masculinizing effects.

How are these drugs used?
To treat hypogonadism: Sometimes men (especially HIV-positive) develop low testosterone levels which can cause symptoms of fatigue, muscle wasting, low (or no) sex drive, impotence, and loss of facial or body hair. This condition is called hypogonadism. Hormone replacement therapy with synthetic testosterone may help to relieve those symptoms.

Women may also develop low testosterone levels and experience symptoms of fatigue, loss of sex drive, and a decreased sense of well-being. Because the androgenic (masculinizing) effects of testosterone and anabolic steroids can be permanent, researchers have been cautious about studying these drugs in women.

To treat weight loss: Anabolic steroids can be used in order to build muscle mass and improve strength and endurance. They can increase the body’s own ability to use protein to make muscle. Anabolics work best when combined with a high-protein diet and regular strength training.

Dosage: Testosterone, whether taken orally or by injection into muscle, is metabolised (broken down) very quickly and efficiently by the liver. New testosterone patches can be applied to the skin, allowing the hormone to be released slowly. Manufacturers of anabolic steroids change the testosterone molecule slightly so that their products are metabolised much more slowly, allowing the effects to last longer with less frequent dosing.

The use of anabolic steroids can raise blood levels of testosterone well above a person’s normal range. As a result, the body may try to regulate testosterone levels by shutting down its own production of testosterone. In order to prevent this, people usually use anabolics in cycles of a few weeks on and then off.

The dosage and cycle should be decided in consultation with a physician. Short cycles (6-8 weeks) are often the most beneficial, in order to minimise potential side effects and maximise potential benefit. Often the most muscle gain occurs in the first month of the cycle.

Side effects
Many of the unwanted side effects of testosterone and anabolic steroids come from their androgenic properties. These drugs can raise blood levels of testosterone, causing side effects which vary from person to person.

The most common side effects in both men and women include increased facial and body hair, oily skin or acne, male pattern baldness, water retention, joint stiffness, erythropoesis (increased red blood cell production) and soreness at the injection site. Laboratory tests show increased levels of liver enzymes. A deepened or hoarsened voice, growth of the clitoris, and menstrual irregularities have been reported in women. The masculinizing side effects may be irreversible in women, even with short term use.

At higher doses over longer periods, increased or decreased sex drive, mood swings, aggressive behaviour, persistent painful erections, shrinking testicles (testicular atrophy), and breast growth (gynecomastia) have been reported in men. Long term use of high dose anabolics can damage the liver, causing jaundice, hepatitis, bleeding and possibly cancer!

Products
There are a vast amount of testosterone products available from many different manufacturers. The most common prescription testosterone products are listed here. Following it is a more comprehensive list of testosterone drugs which are available.

Testosterone cypionate (sold as Depo-Testosterone Cypionate): Depo-Testosterone Cypionate is sustained longer in the body than most other anabolic steroids. A single injection of 200-400mg is given once every 2-4 weeks, then a rest period of 4 weeks, followed by another injection once every 2-4 weeks.

Transdermal testosterone (the “patch”): Testosterone patches allow a slow, steady release of the hormone into the body. The Testoderm patch is applied daily to a man’s shaved scrotum. The newer Androderm patch can be applied daily to the upper arms, back, thighs, or abdomen.

An interesting study into the use of the test. patch was done by Miller and colleagues. They conducted a 12-week pilot study of an experimental low-dose testosterone patch for women. Fifty-three HIV-positive women who had lost about 10% of their normal body weight, and whose blood levels of testosterone were below the normal reference range took part in the study. They were randomly assigned to receive either a placebo patch, a patch releasing 150 micrograms of testosterone daily, or a patch releasing 300 micrograms of testosterone daily. Although the patches restored testosterone levels to normal, only the women who had used the 150 microgram patch gained weight. Unfortunately, all of the weight gained was fat, not muscle mass.

Nandrolone decanoate (sold as Deca-Durabolin): Deca-Durabolin is probably the most popular anabolic used (not just in medicine!) in the treatment of HIV-related weight loss. It has a low rate of side effects and a high anabolic effect. The drug is given by injection into a muscle, at doses ranging from 50-200 mg, every 2-4 weeks for up to 12 weeks. After four weeks off the drug, another cycle of treatment can be started. The androgenic side effects of Deca-Durabolin are much milder than those of testosterone.

At doses of up to 100 mg every 3-4 weeks for up to 12 weeks, women may be able to use this drug. If any changes in menstrual periods occur, the drug should be stopped until the cause of such changes is discovered.

Oxandrolone (Oxandrin): This is an oral anabolic steroid. The androgenic effects are very low and side effects are few. The dosage for men is generally 15-40 mg daily and for women 5-20 mg daily.

Other Testosterone Products: AndroGel, Anadrol, Anapolon, Andriol, Androderm, Androstanolone, Deca-Durabolin, Dianabol, Durabolin, Dynabolon, Equipoise, Finaject, Finaplix, Laurabolin, Masteron, Methandriol, Methandriol Dipropionate, Methyltestosterone, Omnadren 250, Orabolin, Parabolan, Primobolan Depot, Primobolan Tablets, Primoteston Depot, Proviron, Sustenon, Stanazol, Stanozolol, Sten, Synthroid, Synovex, Testosterone Enanthate, Testosterone Heptylate, Testosterone Propionate, Testosterone Suspension, Testosterone Theramex, Testoviron Depot, Winstrol Depot and Winstrol Tablets.

Thyroid Hormones

Thyroid Stimulating Hormone
Thyroid-stimulating hormone (also known as TSH or thyrotropin) is a hormone produced by thyrotropes in the anterior pituitary gland which controls the endocrine function of the thyroid gland.

The hypothalamus produces thyrotropin-releasing hormone (TRH) which stimulates the pituitary gland to release TSH. TSH stimulates the thyroid gland to secrete the hormones thyroxine (T4) and triiodothyronine (T3). The production of TSH is inhibited by the production of somatostatin by the hypothalamus. T3 and T4 also inhibit TSH production and secretion, creating a regulatory negative feedback loop.

The thyroid hormones, thyroxine (T4) and triiodothyronine (T3), are tyrosine-based hormones produced by the thyroid gland. They increase the BMR, affect protein synthesis and increase the body’s sensitivity to catecholamines (such as adrenaline). An important component in the synthesis is iodine.

The major form of thyroid hormone in the blood is thyroxine (T4). This is converted to the active T3 within cells by an enzyme called deiodinase.

Most of the thyroid hormone circulating in the blood is bound to transport proteins: thyroid binding globulin (TBG); Thyroid binding prealbumin (TBPA); this protein is also responsible for the transport of retinol, and so now has the preferred name of transthyretin (TTR); albumin

Only a very small fraction of the circulating hormone is free (unbound); T4 0.03% and T3 0.3%. This free fraction is biologically active, hence measuring concentrations of free thyroid hormones is of great diagnostic value. These values are referred to as fT4 and fT3. Another critical diagnostic tool is the amount of TSH that is present; from these measurements you can determine whether someone is suffering from hypothyroidism or hyperthyroidism.

When thyroid hormone is bound, it is not active, the amount of free T3/T4 is what is important. For this reason, measuring total thyroxine in the blood can be misleading.

The thyroid hormones are essential to proper development and differentiation of all cells of human body. To various extent they regulate protein, fat and carbohydrate metabolism. However, the most pronounced impact is on utilisation of energetic compounds by human cells.

Thyrotoxicosis or hyperthyroidism is the clinical syndrome caused by an excess of circulating free thyroxine and free triiodothyronine, or both. It is a common disorder and affects approximately 2% of women and 0.2% of men.

Parathyroid Hormone
Parathyroid hormone (PTH) is secreted by the parathyroid glands as a polypeptide containing 84 amino acids.

PTH acts to increase the concentration of calcium in the blood. It does this in three ways. It enhances the release of calcium from the large reservoir contained in the bones; it enhances reabsorption of calcium from renal tubules; and it enhances the absorption of calcium in the intestine (by increasing the production of 1,25-hydroxyvitamin D).

PTH also acts to decrease the concentration of phosphate in the blood, primarily by reducing reabsorption in the proximal tubules of the kidney.

Increased calcium concentration in the blood acts (via feedback inhibition) to decrease PTH secretion by the parathyroid glands. This is achieved by the activation of calcium-sensing receptors located on parathyroid cells.

Excessive PTH secretion is known as hyperparathyroidism, and is often the result of a benign parathyroid tumour (primary hyperparathyroidism) that loses its sensitivity to circulating calcium levels. In chronic renal failure secondary hyperparathyroidism can result.

Insufficient PTH secretion is known as hypoparathyroidism, and is commonly caused by surgical misadventure, autoimmune disorder, or inborn errors of metabolism.

PTH can be measured in the blood in several different forms: intact PTH; N-terminal PTH; mid-molecule PTH, and C-terminal PTH, and different tests are used in different clinical situations.

Nitric Oxide (NO)

Nitric Oxide is a free form gas that is produced in the body and is used by the body to communicate with other cells. The endothelium (inner lining) of blood vessels use NO to signal the surrounding smooth muscle to relax, thus dilating the artery and increasing blood flow. NO also plays a role in erection of the penis. The production of NO occurs when the amino acid L-arginine is converted into L-citruline through an enzyme group known as Nitric Oxide Synthase (NOS).

Recently, supplements have come available to boost NO levels and give the athlete an increased and longer lasting “pump” in the muscles. This increased in blood flow and nutrients to the muscles aids in muscle growth. Most “nitric oxide” supplements contain the amino acid Arginine-alpha-keto-glutarate; a combination of arginine and alpha-keto-glutarate (AKG) which has a synergistic effect on increasing NO levels. There was debate over the NO boosting potential of AKG. Studies showed that AKG on its own was not effective at increasing NO levels. However, when combined with arginine, NO levels were increased.

Pro-Hormones

Pro-hormones are precursors to active hormones. Pro- and Nor- prefixes indicate that the substance is a precursor; for example nor-testosterone or nor-adrenalin. The one of most concern to us here is Androstenedione.

Androstenedione is a 19-carbon steroid hormone (hence the name common name “19-nor”) produced in the adrenal glands and the ovaries as an intermediate (precursor) step in the biochemical pathway that produces testosterone and the oestrogens; oestrone and oestradiol. Some androstenedione is also secreted into the plasma, and may be converted in tissues to testosterone.

The production of adrenal androstenedione is governed by AdrenoCorticoTropic Hormone (ACTH), not by gonadotropins. ACTH, as its name implies, stimulates the adrenal cortex.

Androstenedione is manufactured as a dietary supplement, often called “andro” for short. The substance has similar effects to anabolic steroids when taken as a supplement, allowing users to build muscle mass. There are many versions (derivatives) of “andro” but most are based on Androstenedione. For example Chemisport’s Test-100 THP ether; 5-alpha-androt-1-ene-3-one-17-OLTHP ether and T-Bol 100; 1,4-androstadiene-3, 17-dione/5-alpha-androstane-3, 17-beta diol.