Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8337778 | The Journal of Steroid Biochemistry and Molecular Biology | 2018 | 10 Pages |
Abstract
Estrogen receptors (ERα and β) and androgen receptor (AR) regulate various critical processes during spermatogenesis. Since spermatogenesis is very sensitive to hormonal stimuli and perturbations, it is important to understand the regulation of expression of these receptors by sex steroid hormones. Although many studies have reported deregulation of steroid receptors on endocrine disruption, there is no consensus on the regulation of their expression by steroid hormones during spermatogenesis, and a lack of clear understanding of the mechanism of regulation. Here, we evaluated the receptor expressions in a well-established exogenous estradiol administration model. We then investigated the mechanisms by which the individual receptors regulate their expression by binding to the respective hormone response elements upstream of these receptor genes. By further employing in vitro and in vivo models of ER and AR stimulation or antagonism, we delineated their regulation in a receptor subtype-specific manner. Our results indicate that ERα positively regulates expression of both the ERs; whereas, ERβ and AR negatively regulate expression of both ERβ and AR by direct binding to upstream regulatory regions. The perturbations in the levels of steroid receptors could be an important factor contributing to spermatogenic defects and male sub-fertility after estradiol and ER agonist treatment. Our study delineates the direct contribution of the individual steroid receptors in the regulation of their own expression.
Keywords
BPAPHTPPRIPAEREDPNHBSS2,3-bis(4-hydroxyphenyl)-propionitrileSERMPPTCPASMRTMPPDHTMNaseSRC1RNA polymerase II17β-estradiolDMSORNA pol IIDESCyproterone acetateSpermatogenesischromatin immunoprecipitationBisphenol AtestosteroneGene regulationSilencing mediator for retinoid and thyroid hormone receptorsDiethylstilbestrolDihydrotestosteroneDimethyl sulfoxideandrogen response elementestrogen response elementHank’s balanced salt solutionSelective estrogen receptor modulatormicrococcal nucleaseARECHiPAndrogen ReceptorSteroid receptor coactivator 1Estrogen receptor
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Authors
Anita Kumar, Kushaan Dumasia, Sharvari Deshpande, Sanketa Raut, N.H. Balasinor,