Baptissart Marine, Martinot Emmanuelle, Vega Aurélie, Sédes Lauriane, Rouaisnel Betty, de Haze Angélique, Baron Silvère, Schoonjans Kristina, Caira Françoise, Volle David H
INSERM U 1103, Laboratoire GReD, Campus Universitaire des Cézeaux, TSA 60026, CS 60026, 63178 Aubière Cedex, France.
Université Clermont Auvergne, Université Blaise Pascal, GReD, F-63178 Aubière, France.
Oncotarget. 2016 Apr 12;7(15):19468-82. doi: 10.18632/oncotarget.7153.
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.
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表达，该区含有睾丸间质细胞。在成年期，用FRXα激动剂进行短期治疗（12小时）可通过诱导小异源二聚体伴侣（SHP）来抑制类固醇生成基因的表达。然而，FRXα激活对睾丸病理生理学的影响从未被评估过。我们在此证明，在青春期给小鼠喂食补充了胆汁酸的饮食会导致不育发生率增加。这与生殖细胞分化改变和凋亡增加有关，原因是睾酮水平降低。在分子水平上，除了通过诱导类固醇生成的两个抑制因子Shp和Dax-1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降低睾丸间质细胞对下丘脑-垂体轴的敏感性，而下丘脑-垂体轴是睾丸内分泌功能的主要调节因子。总之，BA-FRXα信号传导是性成熟过程中的关键因素。
