Written by Jose Antonio, Ph.D.
06 April 2007

In the world where endocrinology and bodybuilding collide, there isn’t anything quite as fascinating as the androgen receptor. If you don’t already know, the androgen receptor, or AR for short, is localized in the cytoplasmic compartment of the target cell. Once an androgen binds to the AR, the receptor-hormone complex is translocated to the nucleus resulting in many effects; the most important of these is muscle protein accretion!

So in English, lots of androgen plus lots of AR promotes extreme muscle hypertrophy. However, the exact mechanism of how androgens work isn’t completely known. Heck, what is completely known? I still can’t for the love of Elvis figure out who watches “Queer Eye for the Straight Guy.” I mean, who would admit to watching that? Anyhow, enough of the digression. Let’s look at some wacky manipulations done on my four-legged friend, the ubiquitous rat. 

In a study conducted at the University of South Carolina, rats’ plantaris muscles were “functionally overloaded” for one, three, seven or 21 days.  First a slight explanation of the preceding sentence. The plantaris muscle is a “plantar flexor” muscle. It is a muscle that rats “tip toe” on; in humans, it’s so small as to be insignificant, but in rats, it’s pretty damn big. Scientists like this muscle because it’s easy to find and to dissect and it adapts readily to “functional overload.”

Now the term functional overload is kind of an oxymoron. Get this: The way you functionally overload the plantaris muscle is to remove one of the synergist muscles. In this case, they removed the gastrocnemius muscle. If you were to try this experiment at home (and please don’t), that would be like you removing your soleus muscle in order to make your gastrocs bigger! Now, I don’t about you, but I fail to see how this is “functional” and I also fail to see how this in any way mimics the high-load, intermittent stress imposed during weightlifting. But hey, I’m just another nerd trying to interpret all of this complicated science.

So getting back to the functionally overloaded muscles… A subset of these rats was given nandrolone decanoate (ND) at day zero and then overloaded for three days. The dose given was six milligrams per kilogram body weight. That’s equal to a 545-milligram dose for a 200-pound human. I’d call that a moderate dose. 
They found that the hypertrophied plantaris muscle (from functional overload) had much higher concentrations of AR. In fact, AR increased by 106 percent and 279 percent after seven and 21 days of functional overload, respectively. ND treatment increased AR protein concentration by 1,300 percent compared to controls. But get this: Combined ND plus overload had the same effect on AR as overload alone. 

So what does this all mean? Well, clearly muscle growth is in part regulated by changes in AR, meaning AR goes up as muscles enlarge. Also, androgen, in this case nandrolone decanoate, can also upregulate AR (but not additively with overload). Keep in mind this was a short-term study. What’s the analogous condition in humans who use androgens for years? There is none.  I would suspect that years of androgen use coupled with heavy weight training will upregulate AR significantly and make it easier to gain muscle protein. I mean, look at the behemoths at a national class bodybuilding show. Does it look like they’ve reached a limit in gaining muscle mass? It instead looks like they keep growing and growing and growing. My guess is that prolonged androgen self-administration causes a profound alteration in AR concentration, such that even if you lay off from training, you still can regain that muscle mass very quickly. Is this muscle memory at work? Is muscle memory a function of AR levels? Perhaps. Let’s see what science finds out in the upcoming year!

Selenium Depresses Thyroid Hormone!
Selenium intake, if too high, can result in a drop in serum T3 (triiodothyronine).  Here’s how a group at University of California, Davis, found this out. Remember, the RDA for selenium is 50-100 micrograms (mcg) daily. In this study, healthy men were fed foods that were either high or low in selenium for a 120-day period while confined to a metabolic ward. So this study was very well controlled. Selenium intake for all subjects was 47 mcg/day (close to the RDA) and then changed to either a low selenium intake group (14 mcg/day) or a high group (297 mcg/day). The treatment lasted 99 days. As stated before, serum T3 dropped and thyrotropin (thyroid stimulating hormone) increased in the high-selenium group. Thyrotropin stimulates the thyroid gland to secrete thyroxine. Keep in mind that T3 is made via the breakdown of T4 or thyroxine. 

So, if T3 drops, what will happen? If you answered weight gain, then go to the head of the class, you get an A+ for staying awake and answering the question correctly.  By day 64, the high-selenium group started to gain weight while the low-selenium group started to lose weight. By day 92, the weight changes were significant between the two groups. Fat mass decreased by an average of 3.7 pounds in the low-selenium group. Fat-free mass increased by 2.9 pounds in both groups. Serum triglycerides increased in the high selenium group, indicating a difference in fat metabolism. Otherwise, the groups did not differ with respect to energy intake, metabolic rate, respiratory exchange ratio (a measure of how much fat you oxidize or burn), or urinary nitrogen excretion. 

So, you’re probably thinking that the drop in T3 caused the weight gain. Well, if that’s the case, why was metabolic rate and respiratory exchange ratio the same between groups? According to the study’s authors, “We cannot rule out the possibility that high selenium intakes decrease anxiety, leading to less voluntary activity (“fidgeting”), a positive energy balance and weight gain, or vice versa.” 

Another odd thing is why both groups gained fat-free mass. Go figure that one. Regardless of the cause, however, this study does show that you ought to limit your selenium intake. If you take too much, it will adversely affect T3 levels. I could only suspect that in the very long run, that’ll make it easier for you to gain fat.