Polyamines, androgens, and skeletal muscle hypertrophy

Abstract

The naturally occurring polyamines, spermidine, spermine, and their precursor putrescine, play indispensible roles in both prokaryotic and eukaryotic cells, from basic DNA synthesis to regulation of cell proliferation and differentiation. The rate-limiting polyamine biosynthetic enzymes, ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase, are essential for mammalian development, with knockout of the genes encoding these enzymes, Odc1 and Amd1, causing early embryonic lethality in mice. In muscle, the involvement of polyamines in muscle hypertrophy is suggested by the concomitant increase in cardiac and skeletal muscle mass and polyamine levels in response to anabolic agents including β-agonists. In addition to β-agonists, androgens, which increase skeletal mass and strength, have also been shown to stimulate polyamine accumulation in a number of tissues. In muscle, androgens act via the androgen receptor to regulate expression of polyamine biosynthetic enzyme genes, including Odc1 and Amd1, which may be one mechanism via which androgens promote muscle growth. This review outlines the role of polyamines in proliferation and hypertrophy, and explores their possible actions in mediating the anabolic actions of androgens in muscle.