Fxralpha gene is a target gene of hCG signaling pathway and represses hCG induced steroidogenesis

J Steroid Biochem Mol Biol. 2019 Nov:194:105460. doi: 10.1016/j.jsbmb.2019.105460. Epub 2019 Aug 27.

Abstract

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.

Keywords: FXRα; Leydig; Steroidogenesis; Testis; hCG signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Chorionic Gonadotropin / pharmacology*
  • Male
  • Mice, Inbred C57BL
  • Phosphoproteins / genetics
  • Progesterone / metabolism
  • Receptors, Cytoplasmic and Nuclear / genetics*
  • Receptors, LH / genetics
  • Signal Transduction / drug effects
  • Testis / drug effects*
  • Testis / metabolism
  • Testosterone / blood
  • Testosterone / metabolism

Substances

  • Chorionic Gonadotropin
  • LHCGR protein, mouse
  • Phosphoproteins
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, LH
  • steroidogenic acute regulatory protein
  • farnesoid X-activated receptor
  • Testosterone
  • Progesterone