In order for a hormone such as testosterone (the major natural androgen produced by the testicles) to have a biological effect, it must have access to functional receptors. You have all heard the "key in the lock" analogy to decribe hormone-receptor binding. The hormone binds to the receptor by having a complimentary shape, similar to the way a key fits into its lock. If the hormone is an agonist, when it joins with the receptor, it causes the receptor to be activated and signal the interior of the cell. If the hormone is an antagonist, it fits into the receptor, but does not activate it....in other word the key fits the lock, but will not turn. Therefore no signal is sent, and while that receptor is occupied with the antagonist, it can't be occupied and activated by an agonist.

It has been shown that testosterone's acts as an agonist on the one defined androgen receptor (AR) type to provide both the anabolic and androgenic actions; and it has also been shown that androgens act on the glucucorticoid receptor (GCR) as an antagonist, thereby blocking the catabolic effects of cortisol (the major GC) on muscle. More on that later.

Okay, that's most of the jargon out of the way, but it will come in handy shortly. Back to testosterone.... we all know the more you put in, the greater the effect. But what is not so well known, is that the biological response to a certain dose is determined just as much by the level of androgen receptors as by what the dose of androgen is. 70mg/wk of test. is what the body natuarally produces. But, reasearch and experience has shown that that there is a definate dose response curve...the more androgens you take, the higher your lean body mass.

In fact if you don't take several times the physiological level, you won't even notice a response. Most of the early studies on anabolic steroids used doses of, for example, 10mg dianabol per day which is the recommended dose for androgen replacement in hypogonadal males. In normal males however, you only see results at around 30 - 40 mg dianobol per day. Now if all the androgen receptors were occupied at 10mg per day, the response to 40mg per day would not be any greater than the response to 10mg per day.

The point is, that the receptor levels do decrease as the dose increases, but to what extent, is unknown. I checked out the scientific litereature on androgen receptor downregulation, and the only study of any relevance showed that endurance trained rats had higher AR levels than sedentary controls. WHICH GOES TO SHOW YOU, IF YOU HAVEN'T BEEN BUSTING YOUR BUT IN THE GYM FOR A LONG TIME, AS IS NOT GOING TO HELP YOU, you don't have the receptor sites for it. The study also showed that androgen (AS) administration lowered receptor levels in both groups. It has been suggested that the great response almost everyone experiences on their first course may be due to fact that the receptors have not yet been downregulated by previous cycles. That means your receptor sites can either wear out, or simply disappear. I personally think that adrogens wear out their receptor cells and no longer allow the "lock" to be turned by the "key." Since your own receptor cells don't wear out under normal conditions, maybe it's the fact that other steroids are synthetic. I mean, maybe if you got the hormone from another human, your receptors would always stay fresh. It makes sense to me, it's like you putting on your girlfriend's shirt; it will work, but it won't fit the same for her anymore. I don't know how true that is but most of the empirical data suggest there may be something to that.

If any of you have heard of the mythical receptor mapping that is spoken about from time to time, consider this. If you want to donate a slice of muscle, I can tell you what your receptor levels are like. That's easy, but you can't tell anything about receptor sites from a blood test. Also the receptor levels will vary between different muscles. I think that is an interesting fact as well.

To summarise the whole course of events, when androgens are injected, they bind to carrier proteins in the blood. Different angrogens will have varying affinity levels for the carrier proteins. Carrier protiens are our enemy, we want our androgens to be free. Ideally, we would want an androgen with low binding affinity for the carrier proteins so that more of it will circulate as free or unbound form; only active, free androgens are able to bind to receptors. The free androgen then binds to androgen receptors also with different affinities dependant. Here we want high binding affinity.

The number of functional receptors is just as important as the doseges of gear in determining the biological response. Androgens can act as either agonists on AR, or as antagonists on GCR or both (best). Interestingly it appears that the molecular changes required to make an anabolic steroid orally active also increases the binding and antagonism of the GCR (again, the main GCR being cortisol). Ironically, it is not good to totally inhibit the GCR, because when this was done as with the abortion pill, RU486 (GC antagonist) the anobolic effects of gear were no longer seen in rats (see refrence 4). GC's have nessassary functions in the body.
I'll post a thread about what happens after the AR is bound and activated, the so-called post-receptor mechanisms later on...

1. Celotti,F. and Negi Cesi,P. 1992. Anabolic Steroids: A review of their effects on the muscles, of their possible mechanisms of action and of their use in athletics. Journal of Steroid Biochemistry and Molecular Biology; Vol 43, No. 5, pp 469-477.

2. Danhaive,P.A. and Rousseau,G.G. 1986. Binding of glucocorticoid antagonists to androgen and glucocorticoid hormone receptors in rat skeletal muscle. Journal of Steroid Biochemistry; Vol 24, No. 2, pp 481-487.

3. Fernandez,L. et al. 1994. Stanozolol, unlike natural androgens, interact with the low affinity glucocorticoid-binding sites from male rat liver microsomes. Endocrinology Vol 134, No. 3, pp 1401-1408.

4. Danhaive,P.A. and Rousseau,G.G. 1988. Evidence for sex-dependant anabolic response to androgenic steroids mediated by muscle glucocorticoid receptors in the rat. Journal of Steroid Biochemistry; Vol 29, No. 6, pp 575-581.

5. Forbes,G.B. 1985. The effect of anabolic steroids on lean body mass: the dose response curve. Metabolism; Vol 34, No.6, pp 571-573.

6. Inoue K et al. 1993. Rapid increase in the number of androgen receptors following electrical stimulation of the rat muscle. European Journal Of Applied Physiology; Vol 66, pp 134-140.