| Title | Gonadotropin releasing hormone-mediated phosphorylation of estrogen receptor {alpha} contributes to fosB expression in mouse gonadotrophs. | | Author(s) | Chen J, An BS, Cheng L, Hammond GL, Leung PC | | Institution | Department of Obstetrics and Gynecology, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia, Canada V6H 3V5; Shanghai Institute of Planned Parenthood Research. | | Source | Endocrinology 2009 Jul 2. | | Abstract | Estrogen receptors (ERs) are activated by their ligands as well as by signaling pathways that alter ER phophorylation in response to peptide hormones and growth factors. In pituitary gonadotrophs, gonadotropin releasing hormones (GnRHs) act via the type I GnRH receptor (GnRHR). Both GnRH subtypes (GnRH-I and GnRH-II) activate an estrogen response element (ERE)-driven luciferase reporter gene in LbetaT2 mouse pituitary cells, and GnRH-I is most potent in this regard. Moreover, antide (a GnRH antagonist) and a GnRHR siRNA abrogate this effect, while an ERalpha antagonist (ICI 182,780) does not. The ERalpha in LbetaT2 cells is phosphorylated at Ser(118) in the nucleus and at Ser(167) in both nucleus and cytoplasm after GnRH treatments, coincided with increased ERalpha binding to its co-activator, the p300/CBP-associated factor (PCAF). Moreover, siRNA-mediated knockdown of PCAF levels attanuated GnRH-induced ERE-luciferase trans-activation in these cells. Most importantly, both GnRH subtypes robustly up-regulated expression of the immediate early response gene, fosB, while co-treatment with ERalpha siRNA or PCAF siRNA attenuated this effect. This appears to occur at the transcriptional level because co-recruitment of ERalpha and PCAF to an ERE within the endogenous fosB promoter was increased by GnRH treatments, as shown by chromatin immunoprecipitation assays. These data demonstrate that GnRH-mediated phosphorylation of ERalpha in mouse LbetaT2 pituitary cells results in its rapid association with PCAF and the transcriptional activation of fosB, and we demonstrate that this in turn likely activates other genes in pituitary cells including the follicle-stimulating hormone beta subunit gene. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19574399 |
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