Intracrine and Myotrophic Roles of 5α-Reductase and Androgens: A Review

Historically, the circulation was thought to be the primary source of androgens influencing skeletal muscle. However, a growing body of research indicates that skeletal muscle expresses several androgen-synthesizing enzymes, including 5α-reductase. The intramuscular expression of these enzymes suggests that skeletal muscle is capable of synthesizing bioactive androgens, which could induce myotrophic effects via intracrine action. The aim of this brief review is to discuss recent research related to the intracrine and myotrophic roles of androgens, with particular focus on 5α-reductase as a myotrophic mediator. Included in the review are 17 reviews and 58 original studies that were identified by a systematic review from MEDLINE and deemed particularly relevant to our purpose. Results are summarized to provide an overview of 5α-reductase as a mediator of the myotrophic effects of androgens. In particular, discussions are included regarding androgen biosynthesis and androgen signaling within skeletal muscle, the effects of exercise on intramuscular androgen biosynthesis, and clinical applications of androgens and of a new class of myotrophic agonists termed selective androgen receptor modulator. The ability of several peripheral tissues to synthesize bioactive androgens is well documented in the literature. Herein, we summarize newer studies that demonstrate that 1) skeletal muscle has the capability to synthesize both testosterone and dihydrotestosterone from dehydroepiandrosterone, which is present in abundance within the circulation, and 2) that exercise increases the expression of certain androgen-biosynthesizing enzymes within muscle. Intramuscularly synthesized androgens have the potential to influence skeletal muscle via intracrine action; however, their exact role in skeletal muscle development and maintenance requires further elucidation.