Inserm U1103, Université Clermont Auvergne, CNRS UMR-6293, GReD, F-63001 Clermont-Ferrand, France.
Inserm U1103, Université Clermont Auvergne, CNRS UMR-6293, GReD, F-63001 Clermont-Ferrand, France.
J Steroid Biochem Mol Biol. 2019 Nov;194:105460. doi: 10.1016/j.jsbmb.2019.105460. Epub 2019 Aug 27.
The bile acid receptor Farnesoid-X-Receptor alpha (FXRα), a member of the nuclear receptor superfamily, is well known for its roles in the enterohepatic tract. In addition, FXRα regulates testicular physiology through the control of both endocrine and exocrine functions. The endocrine function of the Leydig cells is mainly controlled by the hypothalamo-pituitary axis viaLH/chorionic gonadotropin (CG). If FXRα was demonstrated to control the expression of the Lhcgr gene, encoding the LH receptor; the impact of the LH/CG signaling on the Fxrα expression has not been defined so far. Here, we demonstrate that hCG increases the Fxrα gene expression through the protein kinase-A signaling pathway. Fxrα is then involved in a negative feedback of steroid synthesis. These data improve our knowledge of the local control of the testicular steroidogenesis with the identification of the link between the hypothalamo-pituitary axis and the FXRα signaling pathway.
法尼醇 X 受体α(FXRα)是核受体超家族的成员,其在肠肝途径中的作用是众所周知的。此外,FXRα 通过控制内分泌和外分泌功能来调节睾丸生理学。Leydig 细胞的内分泌功能主要通过下丘脑-垂体轴通过 LH/绒毛膜促性腺激素(CG)来控制。如果 FXRα 被证明可以控制编码 LH 受体的 Lhcgr 基因的表达;那么迄今为止,还没有定义 LH/CG 信号对 Fxrα 表达的影响。在这里,我们证明 hCG 通过蛋白激酶 A 信号通路增加 Fxrα 基因的表达。然后,Fxrα 参与类固醇合成的负反馈。这些数据通过鉴定下丘脑-垂体轴和 FXRα 信号通路之间的联系,提高了我们对睾丸类固醇生成局部控制的认识。