{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T01:13:11Z","timestamp":1784164391281,"version":"3.55.0"},"reference-count":55,"publisher":"The Endocrine Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,2,1]]},"abstract":"<jats:p>Stimulation of pituitary gonadotropes by hypothalamic GnRH leads to the rapid expression of several immediate early genes that play key roles in orchestrating the response of the gonadotrope to hypothalamic stimuli. Elucidation of the signaling mechanisms that couple the GnRH receptor to this immediate early gene repertoire is critical for understanding the molecular basis of GnRH action. Here we identify signaling mechanisms that underlie regulation of the orphan nuclear receptor Nur77 as a GnRH-responsive immediate early gene in \u03b1T3-1 cells and mouse gonadotropes in culture. Using a variety of approaches, we show that GnRH-induced transcriptional upregulation of Nur77 in \u03b1T3-1 cells is dependent on calcium, protein kinase C (PKC), and ERK signaling. Transcriptional activity of Nur77 within the gonadotrope is regulated posttranslationally by GnRH signaling via PKC but not ERK activity. Surprisingly, neither activation of the ERK pathway nor the transcriptional response of Nur77 to GnRH requires the activity of c-Raf kinase. In corroboration of these results, Nur77 responsiveness to GnRH was maintained in gonadotropes from mice with pituitary-targeted ablation of c-Raf kinase. In contrast, gonadotropes from mice with pituitary deficiency of ERK signaling failed to up-regulate Nur77 after GnRH stimulation. These results further clarify the role of ERK and PKC signaling in regulation of the GnRH-induced immediate early gene program as well as GnRH-induced transcription-stimulating activity of Nur77 in the gonadotrope and shed new light on the complex functional organization of this signaling pathway in the pituitary gonadotrope.<\/jats:p>","DOI":"10.1210\/en.2011-0247","type":"journal-article","created":{"date-parts":[[2011,12,21]],"date-time":"2011-12-21T05:42:52Z","timestamp":1324446172000},"page":"700-711","source":"Crossref","is-referenced-by-count":20,"title":["ERK Signaling, But Not c-Raf, Is Required for Gonadotropin-Releasing Hormone (GnRH)-Induced Regulation of Nur77 in Pituitary Gonadotropes"],"prefix":"10.1210","volume":"153","author":[{"given":"Stuart P.","family":"Bliss","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences (S.P.B., A.M.N., J.X., M.S.R.), College of Veterinary Medicine, Cornell University, Ithaca, New York 14853"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy M.","family":"Navratil","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences (S.P.B., A.M.N., J.X., M.S.R.), College of Veterinary Medicine, Cornell University, Ithaca, New York 14853"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianjun","family":"Xie","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences (S.P.B., A.M.N., J.X., M.S.R.), College of Veterinary Medicine, Cornell University, Ithaca, New York 14853"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Miller","sequence":"first","affiliation":[{"name":"Division of Comparative Pathology (A.M.), New England Primate Research Center, Harvard Medical School, Southborough, Massachusetts 01772"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Baccarini","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunobiology (M.B.), Max F. Perutz Laboratories, University of Vienna, 1030 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark S.","family":"Roberson","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences (S.P.B., A.M.N., J.X., M.S.R.), College of Veterinary Medicine, Cornell University, Ithaca, New York 14853"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071612172241100_B1","first-page":"419","article-title":"GnRH activates ERK1\/2 leading to the induction of c-fos and LH\u03b2 protein expression in L\u03b2T2 cells.","volume":"16","author":"Liu","year":"2002","journal-title":"Mol Endocrinol"},{"key":"2020071612172241100_B2","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1210\/me.2007-0515","article-title":"Welcoming \u03b2-catenin to the gonadotropin-releasing hormone transcriptional network in gonadotropes.","volume":"22","author":"Salisbury","year":"2008","journal-title":"Mol 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