Laboratory models of disease
UPDATE. I defended my dissertation. The final text and a video of the public defense are available here.
Glucocorticoid-induced myopathy, that is, loss of muscle caused by commonly-used drugs such as dexamethasone and prednisone, is an extremely common affliction across the world. Every year, 1% of the Americans receive one of these drugs, and about half of them complain about muscle side effects. Scant medical research suggested that this affliction can be alleviated by co-administration of androgen anabolic drugs. Earlier work in my mentor's laboratory shown that, in rodents, both the glucocorticoid and anabolic agents alter muscle's protein content. Moreover, Dr. Shalender Bhasin co-ordinated some of the first human trials investigating androgens' action on human muscle.
Experiments that I proposed and carried for my scientific doctoral degree indicate that, surprisingly, a significant role in muscle protection may be attributable to androgens' anti-catabolic action. That is, testosterone may protect muscle mass by preventing protein loss. In a sense, this was expected, given that the main action of pharmacological-dose glucocorticoids is an increase in muscle protein degradation. Nevertheless, the findings were surprising, because testosterone is more commonly thought of as an activator of protein synthesis. Future studies should elucidate the relative importance of synthesis and degradation changes for the myoprotective action of testosterone.
Lab findings are described in articles such as:
1. The role of GH and IGF-I in mediating anabolic effects of testosterone on androgen-responsive muscle. Serra C, Bhasin S, Tangherlini F, Barton ER, Ganno M, Zhang A, Shansky J, Vandenburgh HH, Travison TG, Jasuja R, Morris C. Endocrinology, 2011.http://www.ncbi.nlm.nih.gov/pubmed/21084444
2. Testosterone improves the regeneration of old and young mouse skeletal muscle. Serra C, Tangherlini F, Rudy S, Lee D, Toraldo G, Sandor NL, Zhang A, Jasuja R, Bhasin S. J Gerontol A Biol Sci Med Sci, 2013. http://www.ncbi.nlm.nih.gov/pubmed/22499765
3. The effects of Testosterone deprivation and supplementation on proteasomal and autophagy activity in the skeletal muscle of the male mouse: differential effects on high androgen-responder and low-androgen responder muscle groups. Serra C, Sandor NL, Jang H, Lee D, Toraldo G, Guarneri T, Wong S, Zhang A, Guo W, Jasuja R, Bhasin S. Endocrinology, 2013. http://www.ncbi.nlm.nih.gov/pubmed/24105483