Testicular steroidogenesis is locally regulated by androgen via suppression of Nur77

Biochemical and Biophysical Research Communications
Chin-Hee SongKeesook Lee

Abstract

Steroidogenesis in the testis is regulated by a negative feedback mechanism through the hypothalamus-pituitary-testis axis. Recent studies suggest that besides this long-loop regulation, testicular steroidogenesis is also locally regulated by androgen. However, the molecular mechanism behind this additional regulatory pathway has been poorly addressed. In the present study, we demonstrate that liganded androgen receptor (AR) suppresses the transcriptional activity of Nur77 on steroidogenic enzyme gene promoters, affecting testicular steroidogenesis. AR physically interacts and colocalizes with Nur77 in the nucleus in the presence of androgen. AR inhibits Nur77 transactivation by competing mainly with coactivators such as SRC-1 for Nur77 binding. These results suggest that androgen, through binding to AR, directly acts as a signal inhibiting the expression of steroidogenic enzyme genes in Leydig cells, eventually resulting in decreased testicular steroidogenesis. These findings strongly support the hypothesis that androgen acts locally to regulate testicular steroidogenesis, and may provide its action mechanism.

References

Jan 1, 1989·Urological Research·A O BrinkmannA Geurts van Kessel
Feb 1, 1995·Biology of Reproduction·A H Payne, G L Youngblood
Nov 23, 2007·Molecular Endocrinology·Stephen M EackerRobert E Braun
Nov 20, 2008·Reproduction : the Official Journal of the Society for the Study of Fertility·Eun-Yeung GongKeesook Lee

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Citations

Jul 3, 2013·Hormones & Cancer·Lisa K PhilpTanya K Day
Dec 5, 2013·Cancer Investigation·Jianping WuHongbin Song
Mar 13, 2016·Seminars in Cell & Developmental Biology·Qing WenYi-Xun Liu
Jul 1, 2014·Biochimica Et Biophysica Acta·Kondababu KurakulaCarlie J M de Vries
Oct 23, 2012·Developmental Biology·Shannon J GallagherChristopher J Payne
Feb 12, 2014·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Qing LiuJianchun Bian
Mar 10, 2021·Reproduction, Fertility, and Development·A C SantosA C Assis Neto

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