08 April, 2009

Muscle Hypertrophy

ResearchBlogging.orgHaving somewhat recently realized that I don't want to have the awesomely statuesque physique of a stick figure for the rest of my life, I began working out (before and after picture below). I still have no idea how to use most of the equipment in the gym and I'm not going to ask Pikkuveli (="little brother") how to use it just because he has ~130kg of muscle to my paltry ~60kg (we're also the same height: ~2.07m). But I am willing to ask where muscles come from.

So I hit up Current Opinion in Pharmacology and managed to learn something: muscles come from your liver.

Kinda weird, huh?

So here's how it more-or-less works:
1) ghrelin gets made by the fundus of your stomach
2) and binds to GHS-R in the arcuate nucleus of the hypothalamus, which then releases growth hormone in response
3) which travels to the liver and gets it to make up some insulin-like growth factor (IGF-1)
4) which then enters the systemic circulation and
5) acts in concert with local mechano growth factor (MGF) at the skeletal muscle to increase net protein synthesis and myotubule formation

But here's what's really cool and elegant about it: IGF-1 and MGF get made from the same mRNA transcript, just spliced up differently in different tissues.

Figure A: Electron micrograph showing a neuromuscular junction. M = muscle, T = axon terminus, arrow = junctional folds with basal lamina. Scale bar = 3um. Source: Wikimedia Commons.

MGF is produced by skeletal muscle tissue in response to mechanical stress (lifting heavy stuff) and cellular damage (the burn the day after working out) and acts in a paracrine and autocrine manner in and on satellite cells that hang out outside the membrane enveloping the muscle fiber. Satellite cells are mononucleated muscle stem cells. MGF tells them to proliferate and make more of themselves. But in order for this increase in satellite cells to translate into muscle growth, IGF-1 (IGF-1Ea, specifically) has to come along and get the proliferating satellite cells to cross the muscle fiber membrane and merge with each other to form a mature, multinucleated myotubule capable of contracting.

Conveniently enough, MGF levels are increased in skeletal muscle for ~2 days post-workout before tapering off. IGF-1Ea levels are increased for longer than that, so there is a sort of 2-phase muscle growth mechanism at work that smartly regulates itself. If MGF levels didn't taper off, satellite cells would keep proliferating and differentiating to myotubules and we'd drown in overgrowing buffness.

But, it's not quite so simple as that. Skeletal muscles are in a continual state of flux as they tear themselves apart and build themselves back up. The body can stash away amino acids in skeletal muscle or grab them back out as needed to help regulate serum pH. Muscle turnover also helps get rid of old, damaged myotubules and replace them with shiny, new, functionalier ones. Apparently this process takes about 2 weeks (I'm thinking maybe this is a minimum interval for exercise to maintain physique?) and heavily involves myostatin. Natural myostatin knockout mutants include Belgian blue cattle.

Figure B: A Belgian Blue bull (on the right).

Laboratory knockouts of myostatin in mice confirm that no myostatin to help muscle turnover along leads to increased muscle growth, but does not increase strength at all. This is thought to be due to increased accumulation of nonfunctional protein in muscle fibers.

Figure C: Toaster's physique before beginning exercise (left) and after (right).

So right about now my latest MGF pulse should be slowing and hopefully my IFG-1Ea is kicking in to get the new satellite cells that surely must be teeming in my shoulders and triceps fusing into functional new muscle. In the meantime, however, raising my elbows anywhere above shoulder level is rather more painful than I thought it might be. Maybe I shouldn't have done quite so many pull-ups, lat pull-downs, and tricep dips...

GOLDSPINK, G., WESSNER, B., & BACHL, N. (2008). Growth factors, muscle function and doping Current Opinion in Pharmacology, 8 (3), 352-357 DOI: 10.1016/j.coph.2008.02.002


Arikia said...

Getting buff for science eh? Good post Mr. Sunshine :)

PhizzleDizzle said...

i love the before/after pic. :):)

130kg v 60kg is a HUGE difference!!!! zomg!!! i totally concur with you on juniper's comment thread now - how the heck are you related to your humongo brother???

Anonymous said...

Figure B: A Belgian Blue bull (on the right).[citation needed]

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