Laurent Michaël, Antonio Leen, Sinnesael Mieke, Dubois Vanessa, Gielen Evelien, Classens Frank, Vanderschueren Dirk
Laboratory of Molecular Endocrinology, Department of Cellular and Molecular Medicine; Gerontology and Geriatrics, Department of Clinical and Experimental Medicine, KU Leuven; Geriatric Medicine, University Hospitals Leuven, Leuven, Belgium.
Asian J Androl. 2014 Mar-Apr;16(2):213-22. doi: 10.4103/1008-682X.122356.
Bone is an endocrine tissue expressing androgen and estrogen receptors as well as steroid metabolizing enzymes. The bioactivity of circulating sex steroids is modulated by sex hormone-binding globulin and local conversion in bone tissue, for example, from testosterone (T) to estradiol (E2) by aromatase, or to dihydrotestosterone by 5α-reductase enzymes. Our understanding of the structural basis for gender differences in bone strength has advanced considerably over recent years due to increasing use of (high resolution) peripheral computed tomography. These microarchitectural insights form the basis to understand sex steroid influences on male peak bone mass and turnover in cortical vs trabecular bone. Recent studies using Cre/LoxP technology have further refi ned our mechanistic insights from global knockout mice into the direct contributions of sex steroids and their respective nuclear receptors in osteoblasts, osteoclasts, osteocytes, and other cells to male osteoporosis. At the same time, these studies have reinforced the notion that androgen and estrogen defi ciency have both direct and pleiotropic effects via interaction with, for example, insulin-like growth factor 1, inflammation, oxidative stress, central nervous system control of bone metabolism, adaptation to mechanical loading, etc., This review will summarize recent advances on these issues in the fi eld of sex steroid actions in male bone homeostasis.
骨骼是一种内分泌组织，表达雄激素和雌激素受体以及类固醇代谢酶。循环性激素的生物活性受性激素结合球蛋白和骨组织中的局部转化调节，例如，通过芳香化酶将睾酮（T）转化为雌二醇（E2），或通过5α-还原酶将其转化为二氢睾酮。近年来，由于（高分辨率）外周计算机断层扫描的使用增加，我们对骨强度性别差异的结构基础的理解有了很大进展。这些微观结构见解构成了理解性类固醇对男性峰值骨量以及皮质骨与小梁骨转换影响的基础。最近使用Cre/LoxP技术的研究进一步完善了我们从全局基因敲除小鼠中获得的机制见解，即性类固醇及其各自的核受体在成骨细胞、破骨细胞、骨细胞和其他细胞中对男性骨质疏松症的直接作用。与此同时，这些研究强化了这样一种观念，即雄激素和雌激素缺乏通过与胰岛素样生长因子1、炎症、氧化应激、骨代谢的中枢神经系统控制、对机械负荷的适应等相互作用，具有直接和多效性影响。本综述将总结性类固醇在男性骨稳态作用领域中这些问题的最新进展。
