Cholesterol is converted into testosterone by something called the Leydig Cells, which (in men) are located in the testes. To do this, 2 enzymes (cytochrome P450 and 3 and 17 ß-hydroxysteroid dehydrogenases) are required, in addition to cholesterol. When these enzymes interact with cholesterol, they can form Testosterone in your body. Then, after testosterone is produced it can elicit a variety of anabolic and androgenic effects. As previously stated, this is a good thing, because the more testosterone you have circulating, the more muscular you will likely be. So now that we have covered where testosterone comes from, how does the body actually receive the signal to release it from the testes?
At the age of puberty, Gonadatropin Releasing Hormone (GnRH) is released in increasingly large amounts from the Hypothalamus, in turn causing the secretion of Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) from the pituitary, and finally the male gonads (testes) are stimulated by those pituitary hormones (LH and FSH). This in turn causes the release of testosterone (which was produced from cholesterol) into the body.
FSH, although formerly thought to only have a role in production of sperm, actually aids the in regulation of Leydig Cell function, while LH directly aids the Leydig Cells in the testes to synthesize testosterone from cholesterol and thereafter secrete it. The synthesis and subsequent secretion of testosterone then causes a surge in other anabolic hormones such as Insulin Like Growth Factor and Growth Hormone. Simple enough, right?
Oh yeah…I also mentioned something called “Dihydrotestosterone” if you recall. Well, this is actually more androgenic than testosterone, though less anabolic. It is created within the body by an enzyme called 5-alpha reductase. All of this sounds great, right? The body is a testosterone producing machine! Well, it’s not all roses. Remember how your body likes to maintain itself in a way so as to be evolutionarily sound? Well, obviously, if it creates too much testosterone, it’s not going to be able to survive a famine (as it will have too much muscle and not enough fat), so it makes use of something called the “negative feedback loop”.
So, once testosterone is created it has the ability to in turn to undergo various metabolic processes that will inhibit GnRH, which in turn inhibits the secretion of LH and FSH, and that brings a halt to natural testosterone production. This is the negative feedback loop.
One of those metabolic processes is called “aromatization”. This is the conversion of testosterone into Estrogen via the aromatase enzyme. And guess what? The more estrogen you have in your body, the less muscular and more fat you’re going to be. Think of it as the hormonal opposite of testosterone.
The production of estrogen as well as other factors all add up to put a halt to the production of testosterone as well hindering our body transformation efforts. And once testosterone has stopped being produced, it no longer converts to the hormones which send the negative feedback signal, and GnRH eventually begins to do its job again when it senses the need for more testosterone. In this way, your body prevents excess hormones from being secreted and thus maintains homeostasis- the dreaded status quo.
So now we know that we want some testosterone (as much as possible) floating around, but how does it actually do what it does?
Well, testosterone (or any natural as well as synthetic androgen) operates by binding the androgen receptor (AR). Once it binds, it travels to the cell’s nucleus along with another Androgen/Receptor coupling, and initiates its various effects.
Once the androgen arrives in the nucleus, it begins a process known as “gene transcription” which basically means that it delivers a message to your cells. The message can be a variety of things, build more muscle or burn more fat (i.e. transform my body!).
It’s important to note that testosterone and the actions of testosterone and other sex steroids also play an important role with regards to modulating and regulating both the Thyroidal and GH/IGF Axis, as well as having some interaction with the adrenergic system. If you haven’t guessed by now, the four main areas I’m going to focus on are all inter-related.
Now, as previously touched upon, dihydrotestosterone (DHT) is considered androgenic relative to testosterone as it is both essential as well as nearly sufficient for the entire virilization of the male external genital organs. This is why females are cautioned not to handle drugs such as 5a-reducatse inhibitors/ DHT reducers such as finasteride or dutestaride while pregnant. However, DHT is not considered to be anabolic because it is not very active in skeletal muscle (it would be if it weren’t deactivated by 3alphahydroxysteroid dehydrogenase). On the other side of the coin, testosterone is highly anabolic in this regard, being responsible, along with other various hormones and growth factors such as Growth Hormone, IGF, etc… for the growth and maintenance of muscle mass.
Remember that enzyme that deactivates DHT (3a-HSD)? Well, just because DHT is not anabolic per se in muscle tissue, doesn’t mean that it can’t be tweaked and modified to be anabolic. Indeed, most synthetic anabolic/androgenic steroids (AAS) were developed by tweaking either testosterone, DHT, or a version of testosterone which has had a slight modification to the 19th carbon position (the last one being known as 19-nor steroids). These modifications to the base molecules of various AAS were made to meet the various and differing needs of clinical androgen deficiency. And, of course, we (yes, you and I) can use them to meet our body transformation goals.
The various modifications made to androgens make them differ in their anabolic/androgenic potency and ratio, as well as giving some of them unique characteristics with regards to other areas. The 19-nor family, for example are all progestins (i.e. they stimulate the progesterone receptor). This makes them immunostimulating and typically helps them soothe aching joints. Some of the DHT derived steroids, on the other hand will produce a uniquely “dry” look to the physique, and this is because they possess some anti-estrogenic and anti-progestenic abilities. As you may suspect, this could actually make joints ache, in contrast to the soothing capabilities of the 19- nor family. Some steroids in the testosterone family of derivations, such as methyltestosterone and fluoxymesterone are only relatively androgenic and don’t produce much actual muscle gain (despite their very high anabolic ratings) and they are the ones typically indicated for both male and female androgen replacement therapy; while others like the DHT-derived oxandrolone are highly anabolic and produce very little in the way of androgenic effects. So what we have in our arsenal of anabolics is a wide range of varying effects and potencies, as well as special properties- all of which we will exploit in our quest for body transformation (if the chemically enhanced route is one you are going to pursue).
There have been literally hundreds of catalogued synthetic AAS that have been developed throughout the years, although their widely varying modes of action are not completely understood. Surprisingly, although we’ve been studying the human body for two millennia’s, this also holds for the naturally occurring androgens as well- testosterone and DHT. Androgens are able to exert at least some of their actions through binding to the Androgen Receptor (AR) and some of them quite independently of the AR. The androgen attaches to a receptor, forms a homodimer with another Androgen/AR pair, and travels to the cell nucleus, initiates a process known as gene transcription, then travels back to the cell membrane.
You still with me? Basically, we need to think of this like going to a party, alright? Let’s think of the androgen as a car, and the receptor as a parking space, ok? Once the car is parked, the people can get out, go inside to the party, and do their thing. At some point, later on in the night (or the early morning, if you’re like me), the people leave and go back to where they came from. Got it?