Broadening the role of osteocalcin in the hypothalamic-pituitary-gonadal axis

Bone is emerging as a versatile endocrine organ and its interactions with apparently unrelated organs are being more widely recognized. Osteocalcin (OCN), polypeptide hormone secreted by osteoblasts, has been found to exert multiple functions through metabolically active form, uncarboxylated OCN (uOCN). Mounting evidence shown that following binding G-protein coupled receptor 6a (Gprc6a) in the peripheral tissues, uOCN acts on pancreatic β cells increase insulin secretion, muscle white adipose tissue promote glucose lipid metabolism. More strikingly, researchers have surprising role of testicular function facilitating testosterone biosynthesis regulating male fertility via pancreas-bone-gonadal axis. However, detailed functional mechanisms hypothalamic–pituitary–gonadal axis or pancreas–bone–gonadal not fully understood. Besides highlighting regulatory hypothalamus pituitary, we also discuss well female potential clinical implications some reproductive diseases pubertal developmental disorders.