Bile acid-FXRα pathways regulate male sexual maturation in mice.
Bile acid-FXRα pathways regulate male sexual maturation in mice.
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DOI：
10.18632/oncotarget.7153
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发表时间：
2016-04-12
期刊：
影响因子：
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通讯作者：
Volle DH
中科院分区：
文献类型：
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作者：
Baptissart M;Martinot E;Vega A;Sédes L;Rouaisnel B;de Haze A;Baron S;Schoonjans K;Caira F;Volle DH
胆汁酸受体法尼醇-X-受体α（FRXα）是核受体超家族的成员。FRXα在成年睾丸的间质区室中表达，其中含有Leydig细胞。在成人中，FRXα激动剂短期治疗（12小时）通过诱导小异源二聚体伴侣（SHP）抑制类固醇生成基因的表达。然而，尚未评价FRXα激活对睾丸病理生理学的影响。我们在这里证明，在青春期年龄的小鼠喂养的饮食补充胆汁酸显示不孕症的发病率增加。这与睾丸激素水平降低导致的生殖细胞分化改变和凋亡增加有关。在分子水平上，除了通过诱导Shp和Dax-1（两种类固醇生成抑制因子）的表达来抑制基础类固醇生成外，BA-FRXα信号传导的主要作用是通过降低Leydig细胞对下丘脑-垂体轴（睾丸内分泌功能的主要调节因子）的敏感性。总之，BA-FRXα信号是性成熟过程中的关键因素。
The bile acid receptor Farnesol-X-Receptor alpha (FRXα) is a member of the nuclear receptor superfamily. FRXα is expressed in the interstitial compartment of the adult testes, which contain the Leydig cells. In adult, short term treatment (12 hours) with FRXα agonist inhibits the expression of steroidogenic genes via the induction of the Small heterodimer partner (SHP). However the consequences of FRXα activation on testicular pathophysiology have never been evaluated. We demonstrate here that mice fed a diet supplemented with bile acid during pubertal age show increased incidence of infertility. This is associated with altered differentiation and increase apoptosis of germ cells due to lower testosterone levels. At the molecular level, next to the repression of basal steroidogenesis via the induction expression of Shp and Dax-1, two repressors of steroidogenesis, the main action of the BA-FRXα signaling is through lowering the Leydig cell sensitivity to the hypothalamo-pituitary axis, the main regulator of testicular endocrine function. In conclusion, BA-FRXα signaling is a critical actor during sexual maturation.