title: Testosterone-dependent interaction between androgen receptor and aryl hydrocarbon receptor induces liver receptor homolog 1 expression in rat granulosa cells.
abstract: Androgens play a major role in the regulation of normal ovarian function; however, they are also involved in the development of ovarian pathologies. These contrasting effects may involve a differential response of granulosa cells to the androgens testosterone (T) and dihydrotestosterone (DHT). To determine the molecular pathways that mediate the distinct effects of T and DHT, we studied the expression of the liver receptor homolog 1 (LRH-1) gene, which is differentially regulated by these steroids. We found that although both T and DHT stimulate androgen receptor (AR) binding to the LRH-1 promoter, DHT prevents T-mediated stimulation of LRH-1 expression. T stimulated the expression of aryl hydrocarbon receptor (AHR) and its interaction with the AR. T also promoted the recruitment of the AR/AHR complex to the LRH-1 promoter. These effects were not mimicked by DHT. We also observed that the activation of extracellular regulated kinases by T is required for AR and AHR interaction. In summary, T, but not DHT, stimulates AHR expression and the interaction between AHR and AR, leading to the stimulation of LRH-1 expression. These findings could explain the distinct response of granulosa cells to T and DHT and provide a molecular mechanism by which DHT negatively affects ovarian function.
authors.affiliation: Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, Illinois, USA.
authors.forename: Yanguang
authors.initials: Y
authors.lastname: Wu
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Baumgarten
authors.forename: Ping
authors.initials: P
authors.lastname: Zhou
authors.forename: Carlos
authors.initials: C
authors.lastname: Stocco
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D013196:Dihydrotestosterone / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006107:Granulosa Cells / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D011401:Promoter Regions, Genetic; D051381:Rats; D017207:Rats, Sprague-Dawley; D011944:Receptors, Androgen / Q000378:metabolism*; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D013739:Testosterone / Q000378:metabolism*
chemical_list: C417002:NR5A2 protein, rat; D011944:Receptors, Androgen; D018336:Receptors, Aryl Hydrocarbon; D018160:Receptors, Cytoplasmic and Nuclear; D013196:Dihydrotestosterone; D013739:Testosterone