The Intracrine Effects of Anabolic Steroids - Metanolone Promotes Stretch-Induced Intramuscular MGF Expression

Arnold's workout regimen are known to generate a hell lot of wear and tear and actually this could be part of his success formula.

I have to admit that the increase in intra-cellular MGF production is probably not the only, but certainly a new and very important pathway by which anabolic steroids "actively" promote muscle growth. According to a recent study from the Department of Rehabilitation and Physical Medicine, Graduate School of Medical and Dental Sciences at the Kagoshima University in Japan (Ikeda. 2013) anabolic agents such as metenolone which is a naturally occuring, WADA-listed long-acting anabolic steroid with weak androgenic (testosterone or androsterone-like) properties. It is isolated from the glands of pregnant domesticated felines, and is supplied as the acetate ester for oral administration and as the enanthate ester for intramuscular injection. Adult doses for the treatment of aplastic anemia are usually in a range of 1–3 mg/kg per day (Wikipedia).

Stretch-induced muscle growth

For the rodents in the study at hand the scientists did escalate the dosage and pumped roughly 10mg/kg (this is already the human equivalent) into the critters.

Then, the right gastrocnemius muscles were stretched repeatedly by manual ankle dorsiflexion 15 times per minute for 15 min. The contralateral muscles were not stretched as a control. In the control rats (n=6), the gastrocnemius was stretched as for the treatment group, but no metenolone was injected. Twenty-four hours after the procedure, the rats were sacrificed by injection of a lethal dose of sodium pentobarbital and their medial gastrocnemius muscles removed on both sides.

Actually, I suspect the sacrifice would not have been necessary as the extraction of the MGF, or as the scientists call it the "the specific autocrine IGF-I splicing variant mechano-growth factor" is something you can measure from a muscle biopsy. So, the only argument against a human study, is probably the dosage and the general administration of anabolic steroids to human subjects.

Figure 1: Treatment effects on MGF, MyoD, Myogenin (a.u.) in rats w/w/out metenolone injection (Ikeda. 2013)

With the highly significant effects on MGF and the non-significant effects on myoD and myogenin, both of which are involved in the recruitement of new muscle nuclei from the stem cell (satellite cell) pool in the musculature, the result of the study is yet of generic nature and will almost certainly apply to humans as well.

Sketch of a mammalian skeletal muscle fiber - myonucleus (turqouis), mitochondria (blue),  sarcoplasmic rectilium (buff), tubules (orange), myofibrils (pinkish)

Artist: Lesley Skeates. Originally from Gray's Anatomy 29th ed. Elsevier. 2008

Stretch to grow? It's not the act of stretching, but rather the wear and tear to the cells that is interpreted as being worked out heavily that induces muscle growth and most importantly structural adaptation (in other words a "stretch during a lift will do just as well as deliberate stretching). The downstream effects of these intracrine (=confined within the cell itself) reactions go way beyond simply pumping more protein into the existing muscular structure.  In a previous study, Ikeda et al. have already shown that "[e]ither continuous or repetitive short duration stretching of muscles for 1 week increased the mRNA expression levels of MyoD, myogenin, and embryonic MyHC relative to those of unstretched  muscles." (Ikeda. 2003)

The latter are markers for the often hailed activation, recruitment and replenishment of muscle "stem-", or "satellite cells", of which you know from the Muscle Hypertrophy 101 (read it) that they are what allows you to grow beyond the natural limit, a limit that makes the muscle of myostatin negative animals huge, but dysfunctional - a direct result of the structural changes not being able to keep pace with the constant influx of protein (learn more).

And with the effects of MGF being related to the important strength facilitating effects of exercise and the underlying cause of the changes being a simple stretch of the musculature the results put another emphasis on the necessity of the "wear and tear" for your body to make the necessary adaptations to exercise

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Figure 2: Illustration of what you should have learned, if you read all installments of the Intermittent Thoughts on Building Muscle (read summary)

So what exactly is he result of the study then? I guess the elevator pitch is: Study confirms the facilitative role in skeletal muscle restructuring / growth of anabolic steroids. If you want more details, I suggest you go back to the "Intermittent Thoughts on Building Muscle Series" and educate yourself about IGF-1, MGF, GH, testosterone, myostatin and co and their specific roles in skeletal muscle hypetrophy (see "reading assignment).

Figure 2, to the right delivers a sneak peak of what you can expect and if that's not attractive enough, I'd suggest you use the "Preliminary Conclusion - Exercise, mTOR/AKT/MAPK, IGF-1, Testosterone, Estrogen, DHT, Nutrition, Supps & Sleep" (read it) of the series as a cognitive anabolic to promote your interest ;-)

I already hinted at that in a previous paragraph, but I think it's still worth repeating in the bottom line that despite being derived in a rodent study with an "exotic" anabolic agent, there is no question that the results of the study at hand will also be relevant for chemical athletes and little evidence they would not apply to

Your reading assignment for today:

1. IGF-1 and its Splice Variants MGF, IGF-IEa & Co - Are the growths hormones master regulators of muscle growth or just a bunch of cogs in the wheel of skeletal muscle hypertrophy?
   
   
2. IGF-1, TNF-α, IL-15 & Co and the Emerging Role of an Auto-/Endocrine-Immune Axis in Skeletal Muscle Hypertrophy  - How does inflammation factor in, is it beneficial or detrimental?
    
3. Zoning in on "The Big T" - Does testosterone (alone) build muscle?
    
4. Quantifying "The Big T" - Do increases of testosterone, which are well within the physiological range matter?
    
5. Understanding the "Big T" - How does testosterone work? What is its effect on stem cells and how come it makes you leaner?
    
6. Estrogen, Friend or Foe of Skeletal Muscle Hypertrophy? - Which role does estrogen play and why could you SERM away your growth potential, when you (ab-)use tamoxifen or potent aromatase inhibitors?
    
7. Dihydrotestosterone (DHT), The All Things Male Hormone - Will it make you bigger, stronger and faster or just balder, fatter and unhealthier?

References:

• Ikeda S, Yoshida A, Matayoshi S, Tanaka N. Repetitive stretch induces c-fos and myogenin mRNA within several hours in skeletal muscle removed from rats. Arch Phys Med Rehabil. 2003 Mar;84(3):419-23.
• Ikeda S et al. The Effect of Anabolic Steroid Administration on Passive Stretching-Induced Expression of Mechano-Growth Factor in Skeletal Muscle. The Scientific World Journal. 2013: Article ID 313605.