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GnRH is released from the hypothalamus in pulses and GnRH pulse frequency differentially regulates follicle-stimulating hormone (FSH) and luteinizing hormone (LH) synthesis and secretion. The GnRH receptor (GnRHR) is a G protein\u2013coupled receptor that canonically activates G\u03b1\u200aq\/11-dependent signaling on ligand binding. However, the receptor can also couple to G\u03b1\u200as and in vitro data suggest that toggling between different G proteins may contribute to GnRH pulse frequency decoding. For example, as we show here, knockdown of G\u03b1\u200as impairs GnRH-stimulated FSH synthesis at low- but not high-pulse frequency in a model gonadotrope-derived cell line. We next used a Cre-lox conditional knockout approach to interrogate the relative roles of G\u03b1\u200aq\/11 and G\u03b1\u200as proteins in gonadotrope function in mice. Gonadotrope-specific G\u03b1\u200aq\/11 knockouts exhibit hypogonadotropic hypogonadism and infertility, akin to the phenotypes seen in GnRH- or GnRHR-deficient mice. In contrast, under standard conditions, gonadotrope-specific G\u03b1\u200as knockouts produce gonadotropins at normal levels and are fertile. However, the LH surge amplitude is blunted in G\u03b1\u200as knockout females and postgonadectomy increases in FSH and LH are reduced both in males and females. These data suggest that GnRH may signal principally via G\u03b1\u200aq\/11 to stimulate gonadotropin production, but that G\u03b1\u200as plays important roles in gonadotrope function in vivo when GnRH secretion is enhanced.<\/jats:p>","DOI":"10.1210\/endocr\/bqab247","type":"journal-article","created":{"date-parts":[[2021,12,5]],"date-time":"2021-12-05T11:18:49Z","timestamp":1638703129000},"source":"Crossref","is-referenced-by-count":16,"title":["Deletion of G\u03b1q\/11 or G\u03b1s Proteins in Gonadotropes Differentially Affects Gonadotropin Production and Secretion in Mice"],"prefix":"10.1210","volume":"163","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9407-6326","authenticated-orcid":false,"given":"George A","family":"Stamatiades","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Diabetes and Hypertension, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA"},{"name":"University of Crete, School of Medicine, 71500 Heraklion, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chirine","family":"Toufaily","sequence":"additional","affiliation":[{"name":"Dept. of Pharmacology and Therapeutics, McGill University, H3G 1Y6 Qu\u00e9bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han Kyeol","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Hypertension, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Dept. of Pharmacology and Therapeutics, McGill University, H3G 1Y6 Qu\u00e9bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iain R","family":"Thompson","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Hypertension, Brigham and Women\u2019s Hospital, Harvard Medical 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USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Offermanns","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Max Planck Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Boehm","sequence":"additional","affiliation":[{"name":"Experimental Pharmacology, Center for Molecular Signaling (PZMS), Saarland University School of Medicine, 66424 Homburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J","family":"Bernard","sequence":"additional","affiliation":[{"name":"Dept. of Pharmacology and Therapeutics, McGill University, H3G 1Y6 Qu\u00e9bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8237-0704","authenticated-orcid":false,"given":"Ursula B","family":"Kaiser","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, 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