Department of Endocrinology and Metabolism, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
J Endocrinol. 2021 Apr 23;249(2):R43-R51. doi: 10.1530/JOE-20-0203.
Bone is emerging as a versatile endocrine organ and its interactions with apparently unrelated organs are being more widely recognized. Osteocalcin (OCN), a polypeptide hormone secreted by osteoblasts, has been found to exert multiple endocrine functions through its metabolically active form, uncarboxylated OCN (uOCN). Mounting evidence has shown that following its binding to G-protein coupled receptor 6a (Gprc6a) in the peripheral tissues, uOCN acts on pancreatic β cells to increase insulin secretion, and on muscle and white adipose tissue to promote glucose and lipid metabolism. More strikingly, researchers have found a surprising role of uOCN in testicular function to facilitating testosterone biosynthesis and regulating male fertility via a pancreas-bone-gonadal axis. However, the detailed functional mechanisms of uOCN on the hypothalamic-pituitary-gonadal axis or the pancreas-bone-gonadal axis are not fully understood. Besides highlighting the regulatory mechanisms of uOCN in the hypothalamus and pituitary, we also discuss its role in male as well as female fertility and its potential clinical implications in some reproductive endocrine diseases and pubertal developmental disorders.
骨骼正在成为一种多功能的内分泌器官，其与明显无关的器官的相互作用正得到更广泛的认识。骨钙素（OCN）是成骨细胞分泌的一种多肽激素，其代谢活跃形式未羧化骨钙素（uOCN）被发现具有多种内分泌功能。越来越多的证据表明，uOCN 与外周组织中的 G 蛋白偶联受体 6a（Gprc6a）结合后，作用于胰岛β细胞以增加胰岛素分泌，并作用于肌肉和白色脂肪组织以促进葡萄糖和脂质代谢。更令人惊讶的是，研究人员发现 uOCN 在睾丸功能中的一个惊人作用，通过胰腺-骨骼-性腺轴促进睾酮生物合成并调节男性生育能力。然而，uOCN 在下丘脑-垂体-性腺轴或胰腺-骨骼-性腺轴上的详细功能机制尚不完全清楚。除了强调 uOCN 在下丘脑和垂体中的调节机制外，我们还讨论了其在男性和女性生育能力中的作用及其在一些生殖内分泌疾病和青春期发育障碍中的潜在临床意义。
