Showing posts with label myoD. Show all posts
Showing posts with label myoD. Show all posts

Sunday, February 16, 2014

There is Such a Thing As Overtraining, Beware! When IGF-1, MyoD & Myogenin Plummet and MAFbx Gnaws Away Your Muscles, It'll Already be Too Late to Acknowledge

Overtraining is real and it's blocking future and reversing past gains.
I am well aware that somewhere out there in the broscientific spheres of the pseudo-experts on the various bulletin boards of a world people call the Internet statements like "there is no overtraining, just undereating" are not uncommon. And in fact, there is a certain connection between the effects / symptoms we usually associate with overtraining on the one, and the consequences of undereating on the other hand. It's a perfect synergy, if you will - a synergy I have been writing about in the past (suggested read: "The SuppVersity Athletes' Triad Series" | read more), but it's not what the most recent study from the Sao Paulo State University in Brazil is about (Alves Souza. 2014).

Overtraining comes in two forms

If this is not your first visit to the SuppVersity the phrases "sympathetic" and "parasympathetic" overtraining will probably sound vaguely familiar. While the latter is the form of overtraining that develops after weeks of 2-4h of daily cardio-training - usually in the presence of undereating, the former is supposed to occur after heavy lifting sessions and is thus more common in sprint type sports.
Check your training status with a heart rate monitor: In spite of the fact that there is no 100% reliable method to test, whether you're overtraining, the heart rate variability - or rather the way it's changing in the course of a training cycle can give you a good idea of whether you're doing too much, already (learn more in "Are You Overtraining? Two Scientifically Proven Methods to Test Yourself" | Part I, Part II).
In the early phases sympathetic overtraining may feel like being "overstimmed", i.e. similar to the strange agitated weakness caffeine naive individuals may experience after their fourth cup of coffee. That's before a deliberating fatigue will take over, episodes of hypoglycemia during (and after) exercise will occur and your life will start to suck as much as your performance (yes, depression is another symptom of overtraining).

Muscle loss instead of gains

While performance oriented athletes usually pull the emergency break, when the notice that their strength, speed, agility, dexterity and all the other qualities that are relevant for world-class performance decline, Mr. Average Joe and his wife Jane tend to ignore the signs until it's already too late and the hormonal changes, Alvez Souza et al. observed in their latest study have already started to gnaw on their precious muscle mass.
Figure 1: Expression of hyptrophy relevant protein and hormones after 12 weeks of (over-)training, as well as subsequent effects on cross-sectional area (CSA) of plantaris muscle; trained vs. sedentary animals (Alves Souza. 2014)
What you can see in Figure 1 are the consequences of 12 weeks of training, in the course of which, the labrats of the Brazilian researchers were subjected to a 1training program with excessive training
load and insufficient recovery time between bouts using a water jump-exercise model of squatting (Figure 1, right):
"Briefly, rats underwent to consecutive training sessions (5 day/week) that consisted of jumps (repetitions) to the water surface (38 cm deep; approximately 150% of rat body length), carrying an overload strapped to a vest on the animal's chest. Initially, all animals completed a 1-week pretraining (once daily) that consisted of a progressive number of sets (2-4) and repetitions (5-12) with a 30-s rest between each set, and carrying an overload of  50%  body  weight  (BW).  Subsequently,  the  rats  began  the  12-week  training  program,  which consisted of progressive overload corresponding to  60% (1 to 3 week), 65% (4 to 6 week), 70% (7th to 8th week), 80% (9th to 10th week), and 85% (11th to 12th week) of BW." (Alves Souza. 2014)
As Alves Souza et al. point out, they have previously demonstrated that this training protocol is effective in promoting type IIA and IID  fiber  atrophy  in  rat  plantaris  muscle  - as long as it is done in a sane and not the typically Western "more helps more" way that was applied in the study at hand.
Overtraining leads to significant changes in muscle specific hormones and proteins: If you discard the fact that most gymbros don't train legs at all (you know, they play football or soccer, right ;-) the above looks pretty much like the "5-days a week, why don't I grow" regimen of the average self-proclaimed hardgainer, whose consternation about his lack of gains is hardly surprising in view of ...
  • When it comes to IGF-1 looking at systemic levels is not enough - rather than the circulating "full" version of MGF, it's the presence of its local splive-variants like MGF that's actually igniting muscle growth. You can learn more about MGF and other factors that contribute to muscle growth in the "Intermittent Thoughts on Building Muscle" Series | go ahead!
    the upregulation of MAFbx, a muscle protein and that is released if you bath muscles in petri dishes full of glucocorticoids has emerged as a central regulator of skeletal muscle catabolism in previous studies (6, 13, 34),
  • the reduction in MyoD and myogenin and the consequent inability to compensate for the exercise induced damages (let alone build new muscle) due to the lack of satellite cell (=muscle stem cell | learn more) activity,
  • the drop in IGF-1 and it's local splice variants that decline with decreasing systemic levels of IGF-1 and play an (imho) still largely underestimated role in the concert of skeletal muscle hypertrophy (see "IGF-1 and its Splice Variants MGF, IGF-IEa & Co - Master Regulators or a Bunch of Cogs in the Wheel of Muscle Hypertrophy?" | read more)
Although we may still be light-years away from understanding the exact interplay of all these factors, I can tell you one thing for sure: As productive as a short 2-week phase of overreaching may be - don't be fooled to believe that the gains would keep coming if you just kept pushing.
References:
  • Alves Souza et al. "Resistance Training With Excessive Training Load and Insufficient Recovery Alters Skeletal Muscle Mass-Related Protein Expression." Journal of Strength and Conditioning Research (2014). Publish Ahead of Print

Monday, October 28, 2013

The Myostatin Inhibiting & Myogenic Effects of Epicatechin: Cacao & Tea Contain Well-Known But Overlooked Anabolic

Does a flavanol in "real chocolate" help you shed the fat and build the muscle?
If you are like me, you are probably already using cacao to build muscle. Whether the effects of the occasional dark chocolate bar are so profound that you'd notice if you'd skip them, is however questionable. Irrespective of the latest results from Gabriela Gutierrez-Salmean and her colleagues from the University of California, VA San Diego Health Care Systems and the Escuela Superior de Medicina del Instituto Politécnico Nacional at the Seccion de Posgrado in Mexico City present in a soon-to-be-published paper in the The Journal of Nutritional Biochemistry (Gutierrez-Salmean. 2013), by the way.

"Epi" as in "Epistane" (*) was yesterday...

... "epi" as in chocolate epicatechin is the future (*Epistane was the brand name of a "pro-steroid"). This could be the take home message of future follow up studies in human beings, if the results Gutierrez-Salmean et al. observed in isolated rodent and human muscle cells translate to the real world.
Chocolate milk is an outstanding muscle builder, but as you will remember from previous SuppVersity Articles and Facebook News, chocolate milk owes its muscle building prowess to the combination of milk protein and sugar which make it an excellent recovery fuel (Saunders. 2011; Spaccarotella. 2011; Pritchett. 2012) that can easily compete with commercial recovery drinks (Lunn. 2012)
Other than the benficial effects of chocolate milk, which are brought about not by chocolate but by the amino acids and (milk-)sugars in the sweet brew, the myostatin inhibiting effects of chocolate appear to depend exclusively on the flavanol (-)-epicatechin which has been shown in previous studies to
  • produce a +50% increase in exercise capacity in mice (Nogueira. 2011), and
  • improve skeletal muscle structure / mitochondrial capacity in older patients with heart failure and type 2 diabetes (Taub. 2012)
Unfortunately, the total amount of this flavenol in chocolate is not only relatively low, it does also vary according to the type and origin of your cacao (assuming that whatever chocolate product you may be using, does even have real cacao in it).
Figure 1: Relative change in myostatin, Myf5, MyoD and Myogenin levels after incubation of cells from skeletal muscle of young vs. old rodents with (-)-epicatechin (Gutierrez-Salmean)
It is thus by no means guaranteed that you will experience any, not even a non-significant reduction in myostatin, when you increase your chocolate consumption; and let's be honest (!) - the weight you gained on your last "chocolate cycle" was not all muscle, was it?

Additional Read: "The Myostatin <> Clenbuterol Connetion" | read more
As far as the myostatin suppression goes you may even argue that it's a good thing that the myostatin-inhibiting effects of a 90% cacao chocolate bar are negligible. Whe? Well, we all know what happens when you suppress myostatin too much, right? Right! Your muscles will balloon up until they eventually seize working and you will - just like the poor myostatin negative mice, no longer be able to support your own weight.

Ok, so it could in fact be a good thing that the "next anabolic revolution", let's call it Chocobolicwon't make you look like the Belgian Blue bull in the image on the right...

Rigth, that's really a good thing. What's not so good, though is that it would also lack the exciting effects on MyoD, Myogenin (sorry for the typo in Figure 1) and Myf5 and with them the ability for the recruitement of satellite cells and the genesis of new myonuclei (learn more) - exactly those processes that will avoid the loss of skeletal muscle function.

Contrary to the futile "baloon"-like gains in response to an increase in protein synthesis, these "gains" are meant to stay. In fact, the presence of additionally myonuclei could be the explanation about the miraculous rapid muscle (re-)gain in "roid using mice" you've read about just yesterday in the SuppVersity Facebook News... but I am getting off topic, here - if you want to learn more about the said study and never miss news like this again go to and like the SuppVersity Facebook page.

Remember the anti-androgenic effects of green tea catechins I wrote about in September 2011? Well guess what EPI, or here EC, is one of the exceptions to the rule that has been shown to increase testeosterone by up to +24% (EC) | learn more
So what's the verdict then? If it were not for dosing and delivery issues, the study at hand would be pretty exciting. It does after all provide evidence that most of us have been consuming tiny amounts of an effective and above all potentially side effect-free myostatin inhibitor for years.

There is still a long way to go from rodent and human myocytes in the petri dish to the average supplement costumer and I am not sure whether or not epicatechin will ever make it across the finish line - irrespective of the promising results Noguiera et al. and Taub et al. already observed in rodent skeletal and human heart muscle in response to the provision of 2x 1.0 mg/kg of pure (-)-epicatechin (2x HED 6.5mg; Nogueira. 2011) or dark chocolate and a beverage containing 100 mg of Epi per day for 3 months (Taub. 2012).
References:
  • Gutierrez-Salmean G, Ciaraldi TP, Nogueira L, Barboza J, Taub PR, Hogan M, Henry RR, Meaney E, Villarreal F, Ceballos G, Ramirez-Sanchez I. Effects of (-)-epicatechin on molecular modulators of skeletal muscle growth and differentiation. Journal of Nutritional Biochemistry. Oct. 2013 [accepted manuscript].
  • Lunn WR, Pasiakos SM, Colletto MR, Karfonta KE, Carbone JW, Anderson JM, Rodriguez NR. Chocolate milk and endurance exercise recovery: protein balance, glycogen, and performance. Med Sci Sports Exerc. 2012 Apr;44(4):682-91. 
  • Nogueira L, Ramirez-Sanchez I, Perkins GA, Murphy A, Taub PR, Ceballos G, Villarreal FJ, Hogan MC, Malek MH. (-)-Epicatechin enhances fatigue resistance and oxidative capacity in mouse muscle. J Physiol. 2011 Sep 15;589(Pt 18):4615-31.
  • Pritchett K, Pritchett R. Chocolate milk: a post-exercise recovery beverage for endurance sports. Med Sport Sci. 2012;59:127-34.
  • Saunders MJ. Glycogen replenishment with chocolate milk consumption. Curr Sports Med Rep. 2011 Nov-Dec;10(6):390.
  • Spaccarotella KJ, Andzel WD. The effects of low fat chocolate milk on postexercise recovery in collegiate athletes. J Strength Cond Res. 2011 Dec;25(12):3456-60. 
  • Taub PR, Ramirez-Sanchez I, Ciaraldi TP, Perkins G, Murphy AN, Naviaux R, Hogan M, Maisel AS, Henry RR, Ceballos G, Villarreal F. Alterations in skeletal muscle indicators of mitochondrial structure and biogenesis in patients with type 2 diabetes and heart failure: effects of epicatechin rich cocoa. Clin Transl Sci. 2012 Feb;5(1):43-7.

Saturday, September 7, 2013

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.
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

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
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.

Tuesday, October 23, 2012

When Rodents Squat, Scientists Gain Insights into How Muscles Grow. IGF-1 Response to Exercise Does Matter - Locally, not Systemically, of Course!

You want to build big wheels? Look no further get yourself the "Squat T-Bar" with integrated 15mA electrical 'motivator' (Aguiar. 2012)
"A rodent study investigating strength workouts?" Yeah, I know it does not sound like that would be in any ways news-worthy, but if you take a look at the image on the right, you will immediately realize: This study is different! Instead of using a treadmill or simply stitching down (or rather up) one of the hindlimbs of the rodents to induce a chronic overload on the other one (don't laugh, many rodent studies have done just that), the study at hand (Aguiar. 2012), which is going to be published in the next issue of the International Journal of Sports Medicine, used a not innovative, but unfortunately largely forgotten (or overlooked?) torturing device that has been developed by Japanese researchers roughly 20 years a ago (Tamaki. 2012).

The rodent torture... ah pardon squat rack ;-)

After being fitted with a canvas jacket in a way that would enable the researchers to limit the twisting and flexion of their torsos (no, that was not a weight lifting belt ;-), the 32 male Wistar rats (80 days old, 250–300 g) were suspended in a standard position on their hind limbs and "encouraged" to exercise by "electrical stimulation [...] that was applied to the rat’s tail through a surface electrode"  (Aguiar. 2012).

Using their neat little toy, the eight researchers from the University Estadual Paulista, in Botucatu, Brazil, were able to submit the rats to a relatively realistic progressive resistance training regimen for either 8 or 12 weeks. Three times per week each rodent had to do 4 sets  of squats for 10-12 repetitions at 65-75% of its individual 1-RM (maximal weight the rodent could handle). During the study period, Aguiar et al. adjusted the weights twice a week to ensure the same training intensity throughout the experiment (something I would highly recommend to anyone of you, as well; try to pack on 1.25lbs - 2.5lbs at least every other week).
Figure 1: Body weight, muscle weight (plantaris, only) and food intake relative to body weight of the control (C8, C12) and trained (T8, T12) rats before and after the 8-week (C8, T8) and 12-week (C12, T12) intervention (data adapted from Aguiar. 2012)
As you can see in figure 1, this minimalist approach to leg training lead to an increase in both body weight and muscle weight that may initially look as if it was strongly linear. You do yet have to be careful about statements like that, because (a) the rodents did gain weight irrespective of whether they were training or not (80 day old rats are still growing!), so comparing the four bars next to each other and saying "yep, linear!" is not feasible, because this would mean linear as in not training for eight weeks < training for 8 weeks < not training for 12 weeks < training for 12 weeks, which is obviously nonsensical. That being said, there is simply (b) insufficient data to say anything about the linearity -- after all, we do have only three data points per group.
"All groups started the experiment with similar body weight. There was a significant increase (p < 0.05) in the body weight of the 4 groups in the resistance training program (C8: 35.5 %; T8: 27.7 %; C12: 46.9 %; and T12: 40.1 %) and final body weights were not significantly (p > 0.05) different between groups. Furthermore, no significant (p > 0.05) differences in the weekly food intakes were observed between the groups."(Aguiar. 2012)
What does yet stick out, is that the obviously age-dependent weight gain in the control groups C8 and C12 did not increase the weight of the plantaris muscle to a weight anywhere near to the muscle weight, the rats in the trained groups achieved.

Muscle gains and strength gains went hand in hand

In the rats who were subject to the three-times-per-week exercise regimen, on the other hand, those increases in muscle size went hand in hand with highly significant improvements in 1-RM squat power; While all groups had begun the training protocol with similar absolute 1-RMs of ~450g (that's about 130% body weight, pre) ...
"[...] training for 8 and 12 weeks promoted a significant (p < 0.05) increase in the RM/BW ratio in the T8 (pre- vs. post-training: 35.7 % increase, p < 0.05) and T12 (pre- vs. post-training: 57.1 % increase, p < 0.05) groups, while no statistical (p > 0.05) difference was observed in their respective control groups." (Aguiar. 2012)
Consequently, the ratio of 1-RM to body weight was 36.1 % and 57.7 % higher in the groups who had been training fot the last 8 or 12 weeks than in the lazy controls and the time-effect yielded another +22% increase in strength in those rodents who trained for 12 and not just 8 weeks.
Figure 2: Strength gains (left) and increases in cross sectional area, as well as intramuscular IGF1, myogenin and myoD expression (data adapted from Aguiar. 2012)
Now you may have heard all that before, what really makes this study stand out, however, is the observation of statistically highly significant correlations of intra-muscular IGF1, myogenin and myoD  mRNA expression, which speaks in favor of my previous hypothesis (read up on that in the Intermittent Thoughts on Building Muscle) that muscle growth is triggered, driven and maintained almost exclusively at a local level.

What are myogenin and myoD? Both are myogenic regulation factors with myogenin actually being part of the myoD family of transcription factors that will make stem cells develop into myocytes (myo D is highest in recently activated satellite cells).
So, when you are looking for "hormonal" (or other pro-anabolic) ghosts (Phillips. 2012), it is imperative to look for them right where the spook, or, in this case, the muscle building magic happens. If you do just that (see figure 2) and correlate the intra-muscular mRNA expression of IGF-1, myogenin and myoD, you will find the "ghostly" explanation for strength and size gains, as well as the confounding structural changes in the architecture of the muscle, with corresponding correlations between the increases in muscle cross-sectional area (CSA) of r = 0.85 (p = 0.0001), r = 0.87 (p = 0.0001) and r = 0.88 (p = 0.0001) for myoD, myogenin and IGF-1, respectively.

Fiber type changes take their time and occur only within the type II spectrum

A neat side-finding, which is actually no news, though, pertains to the fiber-type conversions that took place in response to the exercise regimen. Firstly, the scientists confirmed the notion that these changes occur exclusively within a certain fiber type. In other words, while Aguiar et al. observed conversions from the metabollically more flexible type IIX/D to the highly glycolytic (power) IIA type, no conversions of the highly oxidative type I to type II fibers were observed. And though the results would generally suggest that fiber IIX/D-to-IIA type conversion, as they 
"[...] also appear to occur during endurance training in humans, so that it would [be] reasonable to think that any exercise stimulus (e. g., endurance or strength) that is sufficient in duration and/or intensity can potentially induce conversions within the fast fiber population from type IIX/D to type IIA" (Aguiar. 2012),
the time-frame in the course of which these changes took place -- namely 12 weeks -- would confirm that the common fear of strength and endurance athletes could provoke negative structral adaptations from doing a "cardio" or "strength" workout from time actually is actually unwarranted. Neither will the former turn a powerlifter into a weakling, nor will the latter make a marathon runner "bulky". Both powerlifter and marathoner are on the contrary going to benefit from the conditioning effect and increase in strength, respectively -- not to mention the important effects on overall health both and not as mainstream stupidity will tell you only the powerlifter can derive from, figuratively speaking, "killing some game in the other's territory"

Bottom line: More food for intermittent thoughts on building muscle ;-)

Figure 3: Correlations between acute GH (A), free testosterone (B), IGF-1 (C)  and cortisol (D) responses (area under the curve—AUC) and gains in type II fibre CSA (Burd. 2012).
Eventually, this study is an excellent example of a way to design a rodent study in a way that will render its results actually meaningful. And what's more, in this particularly case these results are not just meaningful, but can also help us to make some sense of a couple of things we have not fully understood / appreciated, as of yet.

What I am particularly thinking about here, is the contrast between the in-vitro effects of IGF-1 and the (more or less absent) real-world effects of the IGF-1 response to exercise (=systemic increase), as it was observed by West and Phillips in a 2012 study. In their well-powered longitudinal study, neither the acute increase in systemic testosterone, nor the exercise induced increases in systemic IGF-1 showed significant correlations with the gains in type II CSA in a cohort (n = 56) of young men in response to 12 weeks of resistance training (West. 2012; see figure 3).

Another interesting finding of the West study was that, contrary to the circulating testosterone and IGF-1 levels, GH and cortisol did show direct correlations with increased muscle cross sectional areas in type II fibers.

And while the former correlation may be explained by the influence of growth hormone (GH) on the local expression of IGF-1 (Hameed . 2004), there is another open question left: How does cortisol actually figure in here? I mean, the chronic elevation / exogenous adminstration of cortisol, has been show to do the exact opposite, i.e. it decreases the local IGF-1 mRNA expression (Inder. 2010).

Figure 4: Graphical summary of what you should have learned Intermittent Thoughts on Building Muscle ... you didn't 'cause you are new to the SuppVersity or simply forgot about it? No problem read the preliminary summary and browse the individual chapters here!
What was missing in the Inder study, however, was the exercise component: Working out does not just exert protective effects against the negative side effects of the provision of exogenous "cortisol" (in this case Dexamethason), as they were observed in the afore referenced study by Inder et al., exercise will also lead to profound increases in local IGF-1 mRNA expression (e.g. +60% in Bamann. 2001), despite the fact that it will also increase the release of the falsely vilified anti-inflammatory glucocorticoid, cortisol... acute vs. chronic, local vs. system, peak values and amplitudes vs. plateaus and AUC values - you got to keep all these contrastive, yet complementary pairs in mind, when you are thinking about the endocrine and intracrine (within the cell) mediators of skeletal muscle hypertrophy.... what? Sounds familiar? Well, you must have been following the Intermittent Thoughts on Building Muscle, then ;-)

References:
  • Aguiar AF, Vechetti-Júnior IJ, Alves de Souza RW, Castan EP, Milanezi-Aguiar RC, Padovani CR, Carvalho RF, Silva MD. Myogenin, MyoD and IGF-I Regulate Muscle Mass but not Fiber-type Conversion during Resistance Training in Rats. Int J Sports Med. 2012 Oct 11.
  • Bamman MM, Shipp JR, Jiang J, Gower BA, Hunter GR, Goodman A, McLafferty CL Jr, Urban RJ. Mechanical load increases muscle IGF-I and androgen receptor mRNA concentrations in humans. Am J Physiol Endocrinol Metab. 2001.
  • Ding H, Gao XL, Hirschberg R, Vadgama JV, Kopple JD. Impaired actions of insulin-like growth factor 1 on protein Synthesis and degradation in skeletal muscle of rats with chronic renal failure. Evidence for a postreceptor defect. J Clin Invest. 1996 Feb 15;97(4):1064-75. 
  • Inder WJ, Jang C, Obeyesekere VR, Alford FP. Dexamethasone administration inhibits skeletal muscle expression of the androgen receptor and IGF-1--implications for steroid-induced myopathy. Clin Endocrinol (Oxf). 2010 Jul;73(1):126-32.
  • Phillips SM. Strength and hypertrophy with resistance training: chasing a hormonal ghost. Eur J Appl Physiol. 2012 May;112(5):1981-3-
  • Sculthorpe N, Solomon AM, Sinanan AC, Bouloux PM, Grace F, Lewis MP. Androgens affect myogenesis in vitro and increase local IGF-1 expression. Med Sci Sports Exerc. 2012 Apr;44(4):610-5.
  • Tamaki T, Uchiyama S, Nakano S. A weight-lifting exercise model for inducing hypertrophy in the hindlimb muscles of rats. Med Sci Sports Exerc. 1992 Aug;24(8):881-6.
  • West DW, Phillips SM. Associations of exercise-induced hormone profiles and gains in strength and hypertrophy in a large cohort after weight training. Eur J Appl Physiol. 2012 Jul;112(7):2693-702.