| First Author | van de Stolpe A | Year | 2004 |
| Journal | Mol Endocrinol | Volume | 18 |
| Issue | 12 | Pages | 2908-23 |
| PubMed ID | 15345745 | Mgi Jnum | J:182399 |
| Mgi Id | MGI:5315355 | Doi | 10.1210/me.2003-0446 |
| Citation | van de Stolpe A, et al. (2004) Estrogen receptor (ER)-mediated transcriptional regulation of the human corticotropin-releasing hormone-binding protein promoter: differential effects of ERalpha and ERbeta. Mol Endocrinol 18(12):2908-23 |
| abstractText | CRH-binding protein (CRH-BP) regulates activation of the hypothalamic-pituitary-adrenal (HPA) axis by binding and inhibiting CRH. We investigated for the first time transcriptional regulation of the human CRH-BP promoter using transient transfections. Estrogen receptors (ERs) contributed to ligand-independent constitutive activation of the promoter, whereas in the presence of estradiol ERalpha induced and ERbeta repressed promoter activity in a dose-dependent manner. TNFalpha inhibited promoter induction by ERalpha in the absence and presence of estradiol. Three ERE half-sites in the CRH-BP promoter bound ERalpha and ERbeta in an EMSA, and disruption of ERE half-sites by site-directed mutagenesis abolished ligand-independent induction by ERalpha and ERbeta and promoter enhancement by estradiol-activated ERalpha. Repression by estradiol/ERbeta was unaffected by disruption of ERE half-sites, activating protein 1, cAMP response element, GATA, or nuclear factor kappaB sites, and reversed to promoter induction by estrogen antagonists, tamoxifen and ICI 182,780, suggesting corepressor involvement. In hypothalamic GT1-7 cells, Western blotting demonstrated rapid induction of endogenous CRH-BP expression by estradiol-bound ER, which was inhibited by TNFalpha. We propose a model in which ERs maintain basal CRH-BP expression in pituitary and neurosecretory cells, whereas in the presence of ERalpha estrogen enhances CRH-BP transcription, causing down-regulation of the HPA axis, and nuclear factor kappaB-activating cytokines activate the HPA axis by inhibiting ERalpha. |
