The mutual dependence between bone and gonads.

It has long been known that sex steroid hormones regulate bone mass accrual. This observation raises the testable hypothesis that bone may in turn regulate the synthesis and secretion of sex steroid hormones in one or both genders. This hypothesis is comprised within a more general hypothesis that bone mass, energy metabolism, and reproduction are regulated coordinately. The identification of osteocalcin as an osteoblast-specific secreted molecule allows us to address this question in molecular terms. This review details how the regulation of male fertility by osteocalcin was unraveled, and how osteocalcin signaling in Leydig cells of the testis occurs. It also discusses the implication of this novel mode of regulation of testosterone synthesis observed in males but not in females.