Satellite Cells and Brand Spanking New Muscle

In the first study, researchers found an increase in satellite cell and myonuclear number in normal men receiving Testosterone enanthate. Just so we're clear, this study essentially shows that varying doses of exogenous Testosterone causes satellite cells to fuse to existing muscle tissue, thereby creating new and permanent muscle.

This was a double blind, randomized study consisting of 61 eugonadal men between the ages of 18 and 35. Subjects were randomly assigned to one of five groups which were administered 25, 50, 125, 300 and 600 mg/weekly for a period of twenty weeks. This was of course after they'd received a GnRH agonist in order to suppress endogenous Testosterone production.

They found a statistically significant increase in the number of satellite cells in those men receiving 300 mg and 600 mg/week as compared to baseline. The change was correlated with the increase in both free and total Testosterone. The number of satellite cells from those receiving 600 mg/week was significantly greater than those receiving 125 and 300 mg/week. In other words, it appears as though the increase in satellite cell number is dose-dependent.

As stated previously, there was also a subsequent increase in myonuclear number. Researchers found that those receiving 600 mg/week had the greatest increase in myonuclear number followed by the 300 mg/week group. Only the 300 and 600 mg/week groups demonstrated an increase in myonuclear number as compared to baseline. The change in these numbers was significantly correlated with total Testosterone levels. So, it appears these effects are both dose and concentration-dependent.

With that being said, this and other data helps to support the idea that this formation of new muscle is mediated via agonism of the AR (androgen receptor). In other words, those androgens which bind avidly to the AR – when used over a fair amount of time – are more likely to actually cause the formation of new muscle.

Anecdotal evidence somewhat supports this idea as well. Androgens like methandrostenolone (D-bol) and oxymetholone (Anadrol) are well known for having awesome effects in terms of increasing muscle size, but more often than not, they have more of a reputation for "leaving you with little" upon cessation of use. As I stated in my Steroids for Health 2003 article, this seems to account, at least partially, for the differences in terms of retention of gains.

What does all this mean in the real world? It means androgens like Testosterone, nandrolone, boldenone, oxandrolone, trenbolone, A1E and methenolone may also be useful in that regard. On the other hand, androgens like methandrostenolone, oxymetholone and 4-AD-EC may be better suited for hypertrophy of existing muscle cells.

This isn't to say that those latter androgens don't bind to the AR at all, just that the previously mentioned androgens (trenbolone, Test, etc.) are better suited, as they appear to bind more avidly to the AR. Neither am I implying that those androgens which bind avidly to the AR won't induce hypertrophy of existing muscle tissue, just that they're better suited for activation of satellite cells and the subsequent effects leading to the formation of new muscle cells. (1-5)

Androgens Without the Side Effects!

The second study involves compounds classified as SARM's (Selective Androgen Receptor Modulators). Essentially, these are nonsteroidal compounds which are designed to be more tissue-selective in terms of their effects. In other words, these are compounds which allow one to experience the positive benefits of using androgens while greatly minimizing unwanted side effects. Sounds good, huh?

Essentially, these compounds exert their effects by binding to the AR (androgen receptor) and acting as agonists just as a steroidal androgen would (although it's possible there are other mechanisms behind their anabolic effects.) The difference is their tissue-selectivity, i.e., being able to activate the androgen receptor in skeletal muscle while not interacting greatly with androgen receptors located in other tissues.

This study and others are allowing us – Biotest – to come closer and closer to developing a compound whose anabolic activity greatly exceeds its androgenic side effects that you could use a small enough dose to experience the anabolic effects of the compound and not any of the androgenic side effects. This is why studies evaluating these compounds' structure-activity relationship (SAR) are so important.

Here's some additional data from one recent study. Researchers evaluated the anabolic activity of a few of these compounds as compared to Testosterone propionate in rats. One compound was found to be anabolic at a dose of only 0.3 mg/day. Yet, at this same dosage, it had no effect on LH or FSH and nearly zero effect on the prostate and seminal vesicle!

So, with this compound at least, we've got anabolic activity which is equal to or greater than Testosterone, with no suppression of LH or FSH and nearly no effect on the seminal vesicle and prostate. While this is great news, there's still more research to be done before we can reach the point where we actually have a compound which is many times more anabolic than "T," yet has no effect on LH, FSH, the prostate, etc.

As I said previously, these studies tend to tie in to one another in some way or another. Well, with these compounds, it's possible we could have one designed which is purely anabolic and activates satellite cells while having zero (or very close to zero) androgenic side effects. Long story short: worries about blood lipids, BPH, alopecia (hair loss) etc., will be greatly minimized or nonexistent. (6-8) And that's the way, uh huh uh huh, we like it!

Testosterone: Dose and Concentration Dependent

This last study involves developing a method of predicting the anabolic response in men administered androgens, or in this specific case, Testosterone. Just like the first study, this one was a double blind, randomized study consisting of 61 eugonadal men between the ages of 18 and 35. Subjects were again randomly assigned to one of five groups which were administered 25, 50, 125, 300, and 600 mg/weekly for a period of twenty weeks. Again, this was after they had received a GnRH agonist in order to suppress endogenous Testosterone production.

Essentially, what researchers found was that the dose of Testosterone administered could account for 61 to 65% of the variability in terms of anabolic effects. Age and PSA (Prostate-Specific Antigen) could only explain an additional 3 to 5% variance in terms of anabolic effects. Also of note is that that both free and total Testosterone accounted for 32 to 39% of the variance in terms of anabolic effects. In the end, they found that dose and age were the only two consistent predictors.

The serum Testosterone levels, while important, aren't really a predictor themselves since they're a function of the Testosterone dose employed. So, essentially, you have the dose of Testosterone being the main determinant of the anabolic response in humans. Age appears to have a small role (i.e, 2-5%) so that leaves room for some other possible predictors, which are really up to speculation.

I'm sure the first response from everyone is, "It's genetics" and yes, while that blanket statement will suffice, it's hard to say what the next most important variable would be, perhaps glucocorticoid receptor content, IGF-1 secretion and/or IGF-1 receptor content, myostatin, androgen-receptor content, etc. Nonetheless, this and other data support the idea that the effects on LBM, fat mass, muscle volume (thigh and quadriceps), strength, leg power, hemoglobin, serum IGF-1 and HDL are all dose and concentration-dependent.

The next question is, at what point is this no longer true? Well, it appears that at a dosage of 600 mg/week of Testosterone enanthate, these effects are still dose and concentration dependent. Beyond that, it's hard to say at what dose exactly this is no longer true. While there is of course a point where these effects are no longer dose-dependent, I'd venture a guess that, in most people, once you've gone over 1,000 mg/week the effects are likely no longer dose-dependent. It's pretty rare for these researchers to exceed 600 mg/week so that question may remain unanswered.

I think this also provides further support for the idea that it's unnecessary for one to "work his way up" (pyramiding) in terms of dosages when it comes to anabolic steroid use. (9,10)

References Cited

1) Sinha-Hikim I, Roth SM, Lee MI, Bhasin S. "Testosterone-Induced Muscle Hypertrophy is Associated with an Increase in Satellite Cell Number in Healthy, Young Men." Am J Physiol Endocrinol Metab 2003 Apr 1; E-00370-2002R1

2) Johnson BJ, et al. "Activation state of muscle satellite cells isolated from steers implanted with a combined trenbolone acetate and estradiol implant." J Anim Sci 1998 Nov;76(11):2779-86

3) Thompson SH, Boxhorn LK, Kong WY, Allen RE. "Trenbolone alters the responsiveness of skeletal muscle satellite cells to fibroblast growth factor and insulin-like growth factor I." Endocrinology 1989 May;124(5):2110-7

4) Nnodim JO. "Testosterone mediates satellite cell activation in denervated rat levator ani muscle." Anat Rec 2001 May 1;263(1):19-24

5) Kadi F, Eriksson A, Holmner S, Thornell LE. "Effects of anabolic steroids on the muscle cells of strength-trained athletes." Med Sci Sports Exerc 1999 Nov;31(11):1528-34

6) Yin D, et al. "Pharmacology, pharmacokinetics, and metabolism of acetothiolutamide, a novel nonsteroidal agonist for the androgen receptor." J Pharmacol Exp Ther 2003 Mar;304(3):1323-33

7) Yin D, et al. "Key structural features of nonsteroidal ligands for binding and activation of the androgen receptor." Mol Pharmacol 2003 Jan;63(1):211-23

8) Yin D, et al. "Pharmacodynamics of selective androgen receptor modulators." J Pharmacol Exp Ther 2003 Mar;304(3):1334-40

9) Woodhouse LJ, et al. "Development of models to predict anabolic response to testosterone administration in healthy young men." Am J Physiol Endocrinol Metab 2003 May;284(5):E1009-17

10) Bhasin S, et al. "Testosterone dose-response relationships in healthy young men." Am J Physiol Endocrinol Metab 2001 Dec;281(6):E1172-81