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Publication : Testicular steroidogenesis is locally regulated by androgen via suppression of Nur77.

First Author  Song CH Year  2012
Journal  Biochem Biophys Res Commun Volume  422
Issue  2 Pages  327-32
PubMed ID  22575506 Mgi Jnum  J:184899
Mgi Id  MGI:5426718 Doi  10.1016/j.bbrc.2012.04.161
Citation  Song CH, et al. (2012) Testicular steroidogenesis is locally regulated by androgen via suppression of Nur77. Biochem Biophys Res Commun 422(2):327-32
abstractText  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.
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