Reciprocal interaction between bone and gonads

• The gonads regulate bone growth, maturation and maintenance through the sex steroid hormones.
• A bone-derived hormone, osteocalcin, favors testosterone production by the Leydig cells of the testis.
• Osteocalcin reproductive function is mediated by a G protein-coupled receptor, Gprc6a.
• Potential conservation of the endocrine role of the skeleton in human.
• Disturbances in osteocalcin or its receptor activity are associated to prostate cancer.

The demonstration that the skeleton is an endocrine organ has enriched the physiological importance of this tissue and advanced our understanding of whole-organism homeostasis. Moreover, that bone affects powerful regulators of its own physiology such as glucose metabolism, energy expenditure, gonads and brain, reinforced the concept of interdependence between organs. This notion is particularly true for the interplay between bone and gonads. On one hand, gonads are essential for bone growth, maturation and maintenance via the secretion of the sex steroid hormones. On the other hand, bone returns this favor to the gonads, through the secretion of osteocalcin (Ocn), which promotes testosterone biosynthesis following its binding to Gprc6a, a G-protein-coupled receptor. Moreover, that a loss of function mutation in GPRC6A leads to glucose intolerance and male sterility in human, expands the biological relevance of the endocrine role of the skeleton and suggests to some extent its implication in the onset of reproductive and metabolic human diseases.