Deletion of estrogen receptors reveals a regulatory role for estrogen receptors-β in bone remodeling in females by not in males
Deletion of estrogen receptors reveals a regulatory role for estrogen receptors-β in bone remodeling in females by not in males
复制标题
DOI：
10.1016/s8756-3282(01)00643-3
复制
发表时间：
2002-01-01
期刊：
影响因子：
4.1
通讯作者：
Baron, R
中科院分区：
文献类型：
--
作者：
Sims, NA;Dupont, S;Baron, R
为了确定雌激素受体（ER）α和ER β在雄性和雌性小鼠中骨生长和重塑中的贡献，我们产生并分析了每种受体的完全敲除和双ER敲除。尽管ER的配体的抑制（即，雌激素受体（ER）在女性绝经后或性腺切除术后导致骨转换的灾难性增加和伴随的骨丢失，但一个或两个ER的缺失未能显示出这种效果。ER α的完全缺失导致雄性和雌性动物骨转换减少而非增加，骨小梁体积增加而非减少。ER β缺失导致雄性和雌性动物的不同反应，雄性动物的骨不受影响，雌性动物的骨吸收减少，骨小梁体积增加。相反，两种ER的缺失导致女性骨小梁体积显著减少，这与骨转换减少而非增加相关。最后，ER α而不是ER β的缺失导致雌二醇和/或睾酮循环水平的重大变化，间接影响骨重建和骨量。因此，只有ER α被证明可以调节男性的骨重建，而在女性中，两种受体亚型都影响这一过程，并且至少在基础敲除条件下可以相互补偿。(C)2002年，Elsevier Science Inc. All rights reserved.
To determine the contributions of estrogen receptor (ER)a and ERbeta in bone growth and remodeling in male and female mice, we generated and analyzed full knockouts for each receptor, and a double ER knockout. Although suppression of the ligand to the ERs (i.e., estradiol) after menopause or gonadectomy in females led to a catastrophic increase in bone turnover and concomitant bone loss, deletion of one or both ERs failed to show such an effect. Complete deletion of ERalpha led to a decrease, not an increase, in bone turnover and an increase, not a decrease, in trabecular bone volume in both male and female animals. Deletion of ERbeta led to different responses in males, where bone was unaffected, and in females, where bone resorption was decreased and trabecular bone volume increased. In contrast, deletion of both ERs led to a profound decrease in trabecular bone volume in females, which was associated with a decrease, not an increase, in bone turnover. Finally, deletion of ERalpha, but not ERbeta, led to major changes in circulating levels of estradiol and/or testosterone, indirectly affecting bone remodeling and bone mass. Thus, only ERalpha was shown to regulate bone remodeling in males, whereas in females both receptor subtypes influenced this process and could, at least under basal knockout conditions, compensate for each other. (C) 2002 by Elsevier Science Inc. All rights reserved.