Before reading the following chapters it is vital the reader has a basic understanding of natural testosterone production and its actions. I realize that it is probably pretty boring for many readers but I have also found it is quite necessary foundational knowledge. Besides the obvious, it is kind of fun to find out what else “the boys” can do anyway. I wish to warn any sensitive readers about my writing style: Though some may take offense at my candidness concerning any topic including sexuality (yes, I said the “S” word) I apologize to no one who chooses to read beyond this point. Simply stated, it is my right to freedom of expression and your right to choose not to read on or agree. (Yes, I once received a letter declaring me “perverse” for the words…”the boys became raisins no sun could shrink worse”.)
There are several sex hormones. Some such as estradiol, estrone, and progesterone are sex hormones referred to as estrogens. Androstenedione, androstenediol, and testosterone are referred to as naturally occurring endogenous (made inside the body) androgens. The former group is the prominent hormones in females responsible for the formation of female pattern fat deposits such as in breast, hips, and buttock areas as well as the formation and maturation of the female sex organs. The latter group, Androgens, are the prominent hormones in males that are responsible for characteristics such as a deeper voice, increased muscle and bone mass, facial hair, increased body hair, male sex organ formation and development, and aggressiveness.
*You would think that last characteristic was true of estrogens too, since PMS is a defense for murder! (It is)
Both men and women produce androgens and estrogens. Women’s dominant production is estrogens, and men’s dominant production is androgens. Reverse this and each will take on their counter-parts characteristic to quite some extent. Our main focus for the following chapters is the male androgen testosterone and its almost endless derivatives and esters.
On average, men produce 4-10 mg of testosterone daily. This means that an average male can synthesize 28-70mg of endogenous testosterone weekly. However, before we go on, a basic understanding of other hormones is necessary also.
FEMALE HORMONE SYNTHESIS
(And hormones men share with them) Women produce testosterone without testicles. (DUH!) A woman’s sex hormones are produced starting at the adrenal glands and ovaries. Through a series of conversion enzyme pathways (chemicals that alter the molecular structure of other chemicals) their bodies synthesize the necessary sex, Glucocorticoid, and Mineralocorticoid steroids.
Mineralocorticoid hormones like Aldosterone regulate mineral balances such as electrolytes and their corresponding water retention and release. Aldosterone is responsible to a great extent for the bloated look and edemas women experience during menstruation. Aldosterone release is significantly affected by other hormones such as estrogens. High estrogen levels result in high aldosterone levels, which in turn result in high water retention.
Glucocorticoid steroids are catabolic (tissue wasting) steroids which break down predominantly damaged tissues for repair and subsequent reuse. The catabolized tissues can be reused as an energy source, or as a source of amino acids (proteins) for assimilation into new tissue. Yes, this Borg-like hormone class will assimilate healthy muscle tissue also to maintain homeostasis (a balance between building and tearing down). The main glucocorticoid steroid hormone focused upon for this book long discussion is cortisol due to the fact that it has a profound catabolic effect upon muscle tissue. Before you think, “Why don’t muscleheads just stop all cortisol synthesis somehow and be the next Mr. or Ms. Olympia ?”, let me explain. Their intent is to regulate, not stop, cortisol production. Tissue can not be rebuilt or made bigger and stronger unless it is first damaged and cleared of the waste products created. Cortisol aids in this metabolic process. Without it, anabolic (tissue building) hormones and chemicals would greatly lose their effects (and immune systems would fail to work adequately). So their goal is to allow enough cortisol for proper catabolism and immune function, but not so much as to allow catabolism to become dominant over anabolism. Cortisol activity can also be controlled site-specifically, but that is a complete different issue. Both men and women endogenously (naturally occurring in the body) synthesize mineralocorticoid and glucocorticoid steroids.
MALE HORMONE SYNTHESIS
Males synthesize androgens at a much higher level than females because they have testicles. Testicles are referred to as “testes” and are located in the scrotum. (Hey, I once received a letter asking how to get “testes” and where do they come from. So stop with the “hey stupid” comments) They also produce androgens through biosynthesis due to enzymatic pathways starting from the adrenal glands which are located near the kidneys. Predominantly, the adrenal glands (there are two) produce epinephrine, which is also called adrenaline, but also produce other hormones commonly referred to as prohormones through a biosynthesis processes and due to conversion enzymes. The lion’s share of a male’s androgens are produced by the Leydig’s cells located in the testes. The most active and dominant androgen is testosterone, which is of course the main focus of this discussion.
Testosterone production is governed by the hypothalamus- pituitary -testes -axis referred to hereafter as the “HPTA”. The HPTA has a series of checks and balances all influenced by serum (the fluid part of the blood containing the active hormones which circulate through the body) levels of several hormones and pro-hormones. If testosterone production is too low, the testes signal the hypothalamus to release more leutenizing
hormone-releasing- hormone (LHRH). The circulating LHRH tells the pituitary to release more leutenizing- hormone (LH) and follicle-stimulating-hormone (FSH). When the circulating FSH and LH reach the testes, they signal the Leydig’s cells to produce more sperm and testosterone.
When testosterone levels are too high the testes signal the hypothalamus to release less LHRH…and then “the boy’s” production process decreases or stops. It is quite interesting that elevated estrogen levels can signal a production decrease for androgens, such as testosterone, far more significantly than any androgen. Please, read that again to be sure you understand the basic HPTA function. It does relate heavily to the effects and effectiveness of exogenous (occurring outside the body) AAS use by athletes. THIS IS AN IMPORTANT FUNCTION TO PROTECT!
TESTOSTERONE… WHAT DOES IT DO ?
The main androgen focused upon for this discussion is testosterone. But please realize that almost all synthetic AAS are chemical variants of testosterone and therefore much of the characteristics apply to them as well. (But not all!) Testosterone has two distinct characteristics or effects.
First, its anabolic characteristics (tissue building) which express themselves as increased and accelerated muscle tissue build-up which leads to faster recovery time after training, illness, and injuries, and to a quicker “regeneration” (I hate that word!) of the entire body. This is because an anabolic response leads to the promotion of protein synthesis and tissue repair or increase.
Secondly, androgenic characteristics or effects which are commonly referred to as secondary male characteristics that promote sexual behavior, libido, development and maturing of the penis, body hair, beard growth, deeper voice, aggressiveness, and formation and maturation of sperm. And of course, as any pubescent boy will tell you, increased production of the sebaceous gland and pimples.
As mentioned before, circulatory levels of testosterone also effect HPTA function, so I should not list it as a characteristic unless I also list pretty much every other sexhormone as well.
When discussing the characteristics of testosterone or its androgen cousins and synthetic AAS relatives, it is important to understand the difference between free (or active) testosterone and bound (or inactive) testosterone/AAS (Anabolic/Androgenic Steroids). Bound testosterone is inactive because it is bound to SHBG (Sex Hormone Binding Globulin) and to a lesser degree, albumin. The sex-steroid molecules are bound by SHBG contained in the blood, which prevents them from fitting into their receptors. That will be explained later. Free (unbound/active) testosterone is able to transmit its characteristics because it fits into receptors. Bound testosterone equals about 97-99% of total testosterone circulation while free testosterone equals 1-3% of total testosterone.
That probably does not sound like much, but even 0.1-0.3 mg of free testosterone has a whole lot of individual separate molecules. And 1 molecule can activate every receptorsite it binds to.
Males have a total testosterone reference range of 225-950 ng/dl (nanograms per decaliter). And a free testosterone reference range for males is 1-3% of the total testosterone reference range. Females have a total testosterone reference range of 14-76 ng/dl and a free testosterone reference range of 0.5-1.8 ng/dl.
Bound testosterone can be unbound due to metabolic requirements and different steroid molecules. And both endogenous and exogenous AAS can react differently to SHBG. For this reason some synthetic AAS can alter the ratio for any other free and/or bound androgenic levels. *As can prohormones and some minerals such as zinc, copper, and magnesium.
Most steroid molecules are specific to their respective cell receptors. This means only testosterone/androgen/AAS molecules can fit into (and transmit their respective message) testosterone/androgen receptor-sites. This is due to shape and size much like a key and a lock: Some keys can fit into other locks, but only the right key can fit in and activate the mechanism. Steroid molecules travel through the blood stream and lymphatic system. This means that everywhere blood goes, the molecules are sure to follow. Using muscle cells as an example, testosterone molecules circulate until they come into contact with testosterone/androgen receptor-sites on the muscle cell. Then they lock together and they form a complex called (what else?) a steroid / receptor complex. Now the complex travels to the cell nucleus where it can bond to specific sequences on the nucleic acid sections of desoxyribonucleic acid (DNA). Here is where a transcription happens and a template of the DNA is created, resulting in messenger ribonucleic acid (mRNA). The mRNA exits the cell nucleus and bonds to/with RNA in the liquid part of the cell called the cytoplasm. Here a translation of the message takes place and an increase in protein synthesis occurs. There is a correlating decrease in catabolism as well. This is because testosterone molecules can occupy cortisol receptorsites and block them. Therefore cortisol can not get in to transmit its message. The results are growth! A simple way of looking at this is… you go to someone’s house to deliver a message and their mom relays it exactly so the job gets done. Sorry about the techno-geek info, but it helps later.
*It should be noted that different labs in different places use slightly different reference ranges. As example 300-1000ng/dl is a common male reference range used by my local lab.
AAS INCREASE PHOSPHOCREATINE SYNTHESIS
Those who have used creatine products such as creatine monohydrate or creatine phosphate realize the effects that more creatine can provide. When anabolic/androgenic steroids (AAS) are administered they cause an increase in Phosphocreatine (CP) synthesis. Let me explain why this creatine stuff is such a cool thing.
ATP (Adenosine Triphosphate) is the fuel that your muscles use to actuate contractions. For this to happen ATP must be changed into ADP (Adenosine Diphosphate) so that energy can be released. This in turn allows for muscular contractions. In order to convert ADP back into the energy source ATP phospcreatine (CP) is needed. So the more CP that is available, the greater the regeneration of ADP to ATP and the greater the work capacity of the muscle at an accelerated rate. There was once a belief that elevated cellular CP levels added strength but not size. Obviously this belief was crushed when creatine products hit the supplement market. Increased CP levels also increase cellular glycogen and protein stores (amino acids) in muscle tissue. This action of course AAS do quite well and so do creatine products. So CP also increases cellular size, due to an increase in intercellular nutrient volume.
*Phosphocreatine is the endogenously produced form of creatine, and is often referred to as creatine phosphate or CP.
AAS POSITIVELY EFFECT FAT
AAS have a positive effect upon fat distribution and storage. There are 3 reasons for this. The first reason is that AAS reduce the amount of insulin released in response to nutrient intake and improved insulin sensitivity. This is in part due to an improved CP synthesis rate and other metabolic factors resulting in an athlete’s muscle cells becoming better able to absorb nutrients such as carbohydrates in the form of glucose and glycogen and proteins in the form of amino acids. Insulin is anti-catabolic and anabolic. Great for muscle cells, but it also causes the conversion of glucose into glycerol and then into triglycerides. Insulin can therefore increase fat stores and growth of fat cells. A decrease in insulin release and an increase in insulin sensitivity means better utilization of nutrients for muscle growth.
The second reason AAS effect fat is because testosterone blocks the activity of a fat-synthesizing hormone called lipoprotein lipase. Since lipoprotein lipase is blocked, less can be produced and stored. GH also has this effect.
The third way testosterone affects fat synthesis is not positive. When testosterone levels are elevated, more is converted into estrogens by way of the conversion enzyme aromatase. This is called aromatization, an important word to understand before reading the rest of this book! Estrogen in turn increases female pattern fat deposits and suppresses HPTA function. Atleast estrogen can increase GH production.
AAS EFFECT BLOOD VOLUME
Anyone who has used AAS (anabolic/androgenic steroids) in the past has noted the increased “muscle pump” effect. This is partly due to elevated phosphocreatine (CP) synthesis explained earlier, but also due to an increase in blood volume. Testosterone increases red blood cell production and count by stimulating the red bone marrow. This also up-regulates hemoglobin production. Hemoglobin is an iron containing compound found in the blood that carries oxygen from the lungs to body tissues such as muscle. This results in a larger appearing, more vascular, harder muscle that receives more oxygen and nutrients. This is a potentially a positive aspect to a point since the result is greater training capacity and improved tissue regeneration. Unfortunately excessive increases in red blood cell count can lead to platelet aggregation and blood clots.
*A note of interest here is that a circulatory chemical called fibrinogen causes blood clotting. There is a great deal of evidence supporting the belief that beer and red wine inhibit this chemical. This is not an excuse to get plowed, but moderate ingestion may be a consideration. A common OTC (over the counter) drug utilized as a so-called blood thinner is Asprin. Asprin is a non-specific COX inhibitor (See Prostaglandins for more info) which may also have some negative effects upon PGE-1 and PGF-2. Prostaglandins are important growth factors in the muscle building process.
WHAT HAPPENS AFTER TESTOSTERONE MOLECULES LEAVE RECEPTORS?
After a testosterone (or AAS) molecule has bonded with an androgen receptorsite and delivered its message, it returns to the blood stream. It can either contact other receptor-sites and do it all again, or it can be changed by enzymic reactions into other compounds such as estrogen, androstenediol, etc., or converted into ineffective molecules which are then excreted though urine. The testosterone molecule can also be converted into DHT (dihydrotestosterone). DHT has a higher affinity (attraction) to receptor-sites than testosterone. DHT has strong androgenic characteristics and weak anabolic qualities for the most part. In fact, DHT is about 5-times as androgenic as testosterone. It also loves sebaceous glands, hair follicles, and prostate tissue. This means more acne and oily skin, hair loss on the scalp, and potential growth of prostate tissue if there is an excess of estrogen and the 5-LO enzyme present. The good news is that DHT improves muscle hardness and cannot be aromatized to estrogen. Regardless of type or derivative, all steroid molecules are processed by the liver and hit the toilet eventually.
STEROIDS: GROWTH ON THE CELLULAR LEVEL
Only a few years ago, scientists claimed that all muscular size increases realized from AAS use was due to nothing more than increased water retention. Part of the reason for such idiotic beliefs was the obvious size and strength losses that occurred after AAS were discontinued.
Muscle growth happens by way of 2 mechanisms:
(1) The enlargement of individual muscle cells and muscle fibers via elevated protein synthesis caused by anabolic substances. This is the first growth mechanism and its called hypertrophy. Androgens such as testosterone (endogenous or exogenous) and all AAS have the greatest effect at this level.
(2) The second is called hyperplasia which involves the formation of new muscle cells and fibers. Though hyperplasia has not been proven in humans, there is a great deal of research creating great doubt that it does not. As example…a study involving a group of college students that were untrained, and a group of competitive bodybuilders that were. Obviously the bodybuilders had much larger arm measurements, yet when muscle biopsies were performed on both groups the individual muscle fibers were identical. Since the bodybuilders had significantly “more” fibers, the researchers theorized that they must have experienced hyperplasia.
Another study on power lifters told the story much more clearly. Two groups of highly trained power lifters were divided in two (groups that is). One group had trained life-long steroid free while the other group had an average of 9 years of steroid use. The steroid group had cycled Anadrol-50, Winstrol-V, Primobolan, Deca Durabolin, Masteron, and Proviron off and on in various combinations for that period. The steroid group showed a significant increase in the “number” of muscle fibers when compared to the drug free power lifters. In the steroid group, researchers also noted an increase in the number of muscle cell nuclei and an enhanced proportion of newly formed muscle fibers. These new fibers with more nuclei were formed from satellite-cells. Satellite cells are immature muscle cells. That is HYPERPLASIA.
Another finding that is equally amazing is that the satellite-cells were found to have a higher number of androgen receptors. This means that the new cells/fibers have a greater capacity to use androgens such as AAS. This study showed that the size of the muscle cell reflects the number of cell nuclei. This study also showed that there was an increase in satellite-cell numbers in the steroid group significantly higher when compared to the drug free group.. So what does this all mean?
Intense training with heavy weights creates a stress on muscle fibers and cells high enough to cause hyperplasia and cellular growth. Those who utilize AAS as part of their training protocol accelerate these responses to the training stimuli. The newly formed muscle cells and fibers have a higher content of androgen receptors so AAS work better on these new cells. Since AAS cause an increase in muscle cell DNA and
therefore increases protein synthesis with no increase in catabolism, (actually AAS decrease the normal rate of catabolism) the formation of new cells and fibers is accelerated. Bigger muscles! An important point to add is that years of training intensely can pay off for those who do not give up training without AAS. New fibers added to existing fibers means more fibers that can grow. In theory, this suggests AAS, which are highly anabolic, (protein synthesis) would be advantageous over those providing higher androgen qualities for long term gains. This is, in part, why more lean mass has been retained post-cycle when high anabolic/ low-moderate androgenic steroids were utilized.
* Satellite-cell production and subsequent fiber inclusion are predominantly stimulated by IGF-1 and FGF (See IGF-1 and FGF for more info).