Estrogen Receptor Regulates Male Satellite Cells in a Female, but Not Male, Environment

Skeletal muscle homeostasis is dependent on the satellite cell pool, which is regulated by numerous signaling pathways. Estradiol (E2) function via estrogen receptor alpha (ERα, Esr1) plays an important role in satellite cell regulation in females, being necessary for satellite cell maintenance, proliferation and differentiation. Here we investigate this signaling axis in male satellite cells. Male satellite cells express Esr1 mRNA at similar levels to female satellite cells, and E2 enhances the proliferation of male satellite cell-derived myoblasts in vitro. Deletion of Esr1 specifically in male satellite cells has no effect on satellite cell number, nor on their ability to self-renew after injury, during regeneration, or when transplanted into male hosts. However, Esr1 deletion severely reduces self-renewal of male satellite cells when transplanted into female hosts. These data suggest that male satellite cells are competent for E2-ERα signaling, but that this signaling is not efficacious in the male environment, though E2-ERα signaling does become necessary when the male cells are transplanted into a female environment.