Regulation of male fertility by the bone-derived hormone osteocalcin.
Regulation of male fertility by the bone-derived hormone osteocalcin.
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DOI：
10.1016/j.mce.2013.10.008
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发表时间：
2014-01-25
影响因子：
4.1
通讯作者：
Oury F
中科院分区：
文献类型：
--
作者：
Karsenty G;Oury F
传统上，骨被认为是一种相对静止的组织，只完成机械和支架功能。然而，在过去的十年里，这种关于骨骼的经典观点已经相当大地演变为一幅更复杂的图景。现在很清楚，骨骼不仅是荷尔蒙输入的接受者，它本身也是一个内分泌器官。骨骼通过分泌一种成骨细胞衍生的分子--骨钙素来调节葡萄糖平衡和男性生殖功能。当去羧化时，骨钙素通过与G偶联受体GPRC6A结合，在胰腺β细胞上增加胰岛素分泌，在肌肉和白色脂肪组织上促进葡萄糖稳态，在睾丸间质细胞上促进睾酮的生物合成。最近，研究还表明，骨钙素通过胰腺-骨-睾丸轴发挥作用，该轴独立于和平行于下丘脑-垂体-睾丸轴，通过促进睾酮生物合成来调节男性的生殖功能。最后，在试图将骨钙素的生物学相关性从小鼠扩展到人的过程中，GPRC6A被证明是人类原发睾丸衰竭潜在的新的易感基因。总之，这些结果为骨骼内分泌作用的重要性提供了新的线索，也为寻找这个器官的额外内分泌功能提供了证据。
Traditionally, bone has been viewed as a relatively static tissue only fulfilling mechanical and scaffolding function. In the past decade however, this classical view of the bone has considerably evolved towards a more complex picture. It is now clear that the skeleton is not only a recipient for hormonal input but it is also an endocrine organ itself. Through the secretion of an osteoblast-derived molecule, osteocalcin, the skeleton regulates glucose homeostasis and male reproductive functions. When undercarboxylated, osteocalcin acts following its binding to a G-coupled receptor, GPRC6A, on pancreatic β cells to increase insulin secretion, on muscle and white adipose tissue to promote glucose homeostasis and on Leydig cells of the testis to favor testosterone biosynthesis. More recently, it was also shown that osteocalcin acts via a pancreas-bone-testis axis that regulates, independently of and in parallel to the hypothalamus-pituitary-testis axis, male reproductive functions by promoting testosterone biosynthesis. Lastly, in trying to expand the biological relevance of osteocalcin from mouse to human, it was shown that GPRC6A is a potential new susceptibility locus for primary testicular failure in humans. Altogether, these results shed new light on the importance of the endocrine role of the skeleton and also provide credence to the search for additional endocrine functions of this organ.
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影响因子：
64.5
作者：
Ferron M;Wei J;Yoshizawa T;Del Fattore A;DePinho RA;Teti A;Ducy P;Karsenty G
通讯作者：
Karsenty G
影响因子：
6.2
作者：
Kirmani, Salman;Atkinson, Elizabeth J.;Melton, L. Joseph, III;Riggs, B. Lawrence;Amin, Shreyasee;Khosla, Sundeep
通讯作者：
Khosla, Sundeep
影响因子：
18.2
作者：
通讯作者：
--
DOI：
10.1073/pnas.0404743101
发表时间：
2004-12-07
影响因子：
11.1
作者：
Ma, XP;Dong, YL;Kumar, TR
通讯作者：
Kumar, TR
影响因子：
56.9
作者：
Kousteni, S;Chen, JR;Manolagas, SC
通讯作者：
Manolagas, SC