Steroid Action - Is it in the receptor ?


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By Jose Antonio PHD

Everybody knows that anabolic steroids, or what most researchers call androgens, promote muscular growth and produce a man's characteristic "maleness": facial hair, body hair, heavy musculature and, for some, aggressive behavior. (Since women have much less circulating androgen, the effects would be much more profound if they used these hormones.) But how do men get so big? Most sport scientists say that the receptor for testosterone (the androgen receptor) is fully saturated at normal physiological levels, which means that the average guy has enough circulating androgen to bind to all of his receptor sites.

Don't let this science jargon scare you. Think of hormones — in this case testos-
terone — as a "key." and its receptor as a "lock" to a door. When testosterone binds
to the androgen receptors in skeletal muscle fibers, it's in essence unlocking a door.
When this door is unlocked, certain physiological processes can occur. In the case of
androgen and androgen receptors, the end result is larger muscles.

Now, if enough keys (androgen) exist for every lock (androgen receptor), then giving someone more keys shouldn't unlock any more doors. Or can we possibly make more doors (androgen receptors) for this powerful hormone to open?

Can the Body Manufacture More Androgen Receptors?

Muscle obviously responds to androgens. Some scientists believe that the differences in muscle mass between the sexes is related to levels of the androgen receptor. Men have more and should therefore be sensitized to circulating androgen. It has been postulated that the shoulder (deltoids, trapezius) and pectoral muscles exhibit higher androgen receptor levels in males than in females, which might explain some of the differences in upper-body size between men and women.
A number of researchers believe that if the androgen receptor is saturated at normal physiological amounts, then any excess androgen would only down-regulate (decrease the number or affinity of) the receptor. But androgens don't have the same response in all tissues. For example, a down-regulation of androgen receptors in the penis takes place in response to androgen. It makes sense that as circulating androgens rise in a developing animal, the level of androgen receptors in the penis would decrease along with androgen-induced growth. As the penis reaches adult size, it consequently becomes insensitive to the anabolic effects of androgen.
But is this what occurs in muscle tissue? Probably not. Androgens seem to exert their anabolic effects through multiple mechanisms. One possibility is that if you take exogenous androgen (that is, oral or injectable anabolic steroids), you may actually increase the level of androgen receptors present in skeletal muscle. If you have more receptors, you'd have an enhanced anabolic effect as a result of steroid use.
In some of my rat subjects, the androgen receptor levels are decreased in certain skeletal muscles — when you take away almost all of the animals' normal circulating lestos-terone, they end up with fewer receptors. So guess what happens when you give these rats androgens? They up-regulate, or increase the number of androgen receptors.
Big deal, you say. This is just a bunch of chemistry gob-bledygook. Well, if you've been paying attention, you'll see how this scenario might explain why taking greater and greater doses of androgens produces larger and more muscular bodybuilders. A plateauing effect of androgens doesn't seem to occur: The more you take, the more receptors you make, the more sensitized your muscles become and the bigger you get. It becomes a constant anabolic cycle.
Although not proven scientifically, this may explain some of the profound effects seen with steroid use among bodybuilders.

The Abortion Pill: an Anabolic Agent?

Androgens can bind to other receptors, too. Think of this process as being like having a key that fits really well in one door, but if you jiggle and wiggle it a little you can open other locks as well. For instance, androgens may actually bind with receptor sites for glucoconicoids, which would then have an anticatabolic effect. RU486 (the French abortion pill) has been shown to block the glucocorticoid receptor and have anticatabolic properties in skeletal muscle. In fact, some scientists believe this blocking of anticatabolic receptors to be the most important way in which steroids affect muscle. If that's true you'd think the use of RU486 would be prevalent among serious athletes and bodybuilders, but it isn't.
The bottom line is that androgens may act physiologically through many avenues to produce potent anabolic effects. Given their effects on androgen receptors and their ability to block the effects of muscle-wasting hormones via the glucocorticoid receptor, you're dealing with a very powerful hormone. Just look at today's elite bodybuilders and you'll see what I mean.