Bile acid-FXRalpha pathways regulate male sexual maturation in mice. - Archive ouverte HAL
Article Dans Une Revue Oncotarget Année : 2016

Bile acid-FXRalpha pathways regulate male sexual maturation in mice.

Résumé

The bile acid receptor Farnesol-X-Receptor alpha (FRXalpha) is a member of the nuclear receptor superfamily. FRXalpha is expressed in the interstitial compartment of the adult testes, which contain the Leydig cells. In adult, short term treatment (12 hours) with FRXalpha agonist inhibits the expression of steroidogenic genes via the induction of the Small heterodimer partner (SHP). However the consequences of FRXalpha 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-FRXalpha signaling is through lowering the Leydig cell sensitivity to the hypothalamo-pituitary axis, the main regulator of testicular endocrine function. In conclusion, BA-FRXalpha signaling is a critical actor during sexual maturation.

Dates et versions

hal-01925156 , version 1 (16-11-2018)

Identifiants

Citer

Marine Baptissart, Emmanuelle Martinot, Aurelie Vega, Lauriane Sedes, Betty Rouaisnel, et al.. Bile acid-FXRalpha pathways regulate male sexual maturation in mice.. Oncotarget, 2016, 7 (15), pp.19468--82. ⟨10.18632/oncotarget.7153⟩. ⟨hal-01925156⟩

Altmetric

Partager

More