title: Steroid receptor coactivator-3 is required for progesterone receptor trans-activation of target genes in response to gonadotropin-releasing hormone treatment of pituitary cells.
abstract: Regulation of gonadotropin production involves interplay between steroids and neuropeptides, and we have examined the effects of gonadotropin-releasing hormones (GnRH I and GnRH II) on progesterone receptor (PR) activation in alphaT3-1 pituitary cells. Treatment with GnRHs activated a progester-one response element (PRE)-luciferase reporter gene, and this was blocked by protein kinase C and protein kinase A inhibitors but not by RU486. Treatment with GnRHs phosphorylated the PR at Ser(294) and increased PR translocation to the nucleus within 1 h. Interactions between the PR and several coactivators were examined, and treatment with GnRHs specifically induced PR-steroid receptor coactivator-3 (SRC-3) interactions within 8 h. In chromatin immunoprecipitation assays, recruitment of PR and SRC-3 by the PREs of the luciferase reporter gene or the gonadotopin alpha-subunit gene promoter was also increased by GnRHs within 8 h, while progesterone-induced recruitment of PR to the PREs occurred in association with much less SRC-3. A small interfering RNA knockdown of type I GnRH receptor levels reduced PR activation by GnRHs, while progesterone-dependent PR activation was unaffected. Moreover, small interfering RNA knockdown of SRC-3 abolished PRE-luciferase trans-activation by the PR in response to GnRHs. Collectively, these data indicate that PR activation by GnRHs in alphaT3-1 cells is type I GnRH receptor-mediated and that trans-activation of PR-responsive genes requires SRC-3 in this context.
authors.affiliation: Department of Obstetrics and Gynecology, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia V6H 3V5, Canada.
authors.forename: Beum-Soo
authors.initials: BS
authors.lastname: An
authors.affiliation: Department of Obstetrics and Gynecology, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia V6H 3V5, Canada.
authors.forename: David M
authors.initials: DM
authors.lastname: Selva
authors.affiliation: Department of Obstetrics and Gynecology, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia V6H 3V5, Canada.
authors.forename: Geoffrey L
authors.initials: GL
authors.lastname: Hammond
authors.affiliation: Department of Physiology, Institute of Biomedicine, University of Turku, 20520 Turku, Finland.
authors.forename: Adolfo
authors.initials: A
authors.lastname: Rivero-Muller
authors.affiliation: Department of Physiology, Institute of Biomedicine, University of Turku, 20520 Turku, Finland.
authors.forename: Nafis
authors.initials: N
authors.lastname: Rahman
authors.affiliation: Department of Obstetrics and Gynecology, Child and Family Research Institute, University of British Columbia, Vancouver, British Columbia V6H 3V5, Canada. Electronic address: peleung@interchange.ubc.ca.
authors.forename: Peter C K
authors.initials: PCK
authors.lastname: Leung
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D017930:Genes, Reporter; D007987:Gonadotropin-Releasing Hormone / Q000627:therapeutic use*; D051548:Histone Acetyltransferases; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D015735:Mifepristone / Q000494:pharmacology; D056921:Nuclear Receptor Coactivator 3; D010902:Pituitary Gland / Q000166:cytology / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011980:Receptors, Progesterone / Q000737:chemistry* / Q000235:genetics*; D013256:Steroids / Q000737:chemistry; D013997:Time Factors; D015534:Trans-Activators / Q000502:physiology*; D015533:Transcriptional Activation
chemical_list: D011980:Receptors, Progesterone; D013256:Steroids; D015534:Trans-Activators; D015735:Mifepristone; D007987:Gonadotropin-Releasing Hormone; D008156:Luciferases; D051548:Histone Acetyltransferases; C538867:Ncoa3 protein, mouse; D056921:Nuclear Receptor Coactivator 3