Inhibin and the regulation of bone mass

Inhibins A and B are gonadal peptide members of the transforming growth factor-beta superfamily that serve as negative feedback regulators of pituitary follicle-stimulating hormone (FSH). Accumulating evidence suggests that bone turnover and bone loss increase in women before menopause and the decrease in serum estradiol levels. Increased FSH levels have been correlated with some of these perimenopausal changes, whereas decreased inhibins strongly correlate with increases in bone formation and resorption across the menopause transition, and predict lumbar bone mass in perimenopausal women, likely resulting from the direct inhibin suppression of osteoblast and osteoclast development. Interestingly, continuous exposure of mice to inhibin A in vivo is anabolic and protective against gonadectomy-induced bone loss. Together, these data suggest inhibins contribute to the endocrine regulation of bone metabolism via a bimodal mechanism of action such that cycling inhibin exposure suppresses bone turnover, and continuous exposure to inhibins is anabolic.