“…FSHβ and FSH receptor (FSHR) knockout mice do not undergo bone loss after ovariectomy, 35 nor do rats that have been both hypophysectomized and ovariectomized, 36 supporting the idea that FSH is mainly responsible for ovariectomy-induced bone loss. However, complicating the in vivo analysis, the FSHR knockout mice have an increased level of testosterone, 37 and testosterone (via aromatization to estrogen or testosterone itself ) is protective of bone. 38 Despite the effects of testosterone, FSH acts, in part, directly on osteoclasts, as osteoclasts express the FSH receptor, and respond to FSH in vitro to activate osteoclastogenesis.…”