{"doi":"10.1210/endocr/bqab247","title":"Deletion of Gαq/11 or Gαs Proteins in Gonadotropes Differentially Affects Gonadotropin Production and Secretion in Mice","abstract":"<jats:title>Abstract</jats:title>\n               <jats:p>Gonadotropin-releasing hormone (GnRH) regulates gonadal function via its stimulatory effects on gonadotropin production by pituitary gonadotrope cells. 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–coupled receptor that canonically activates Gα q/11-dependent signaling on ligand binding. However, the receptor can also couple to Gα s 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 Gα s 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 Gα q/11 and Gα s proteins in gonadotrope function in mice. Gonadotrope-specific Gα q/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 Gα s knockouts produce gonadotropins at normal levels and are fertile. However, the LH surge amplitude is blunted in Gα s 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 Gα q/11 to stimulate gonadotropin production, but that Gα s plays important roles in gonadotrope function in vivo when GnRH secretion is enhanced.</jats:p>","journal":"Endocrinology","year":2022,"id":28835,"datarank":0.6156484883852176,"base_score":2.5649493574615367,"endowment":2.5649493574615367,"self_citation_contribution":0.38474240361923057,"citation_network_contribution":0.23090608476598698,"self_endowment_contribution":0.38474240361923057,"citer_contribution":0.23090608476598698,"corpus_percentile":null,"corpus_rank":null,"citation_count":12,"citer_count":9,"citers_with_citation_signal":6,"citers_with_endowment":6,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":160504,"name":"Chirine Toufaily","orcid":null,"position":1,"is_corresponding":false},{"id":160505,"name":"Han Kyeol Kim","orcid":null,"position":2,"is_corresponding":false},{"id":11254,"name":"Xiang Zhou","orcid":"0000-0002-4331-7599","position":3,"is_corresponding":false},{"id":160506,"name":"Iain R Thompson","orcid":null,"position":4,"is_corresponding":false},{"id":160507,"name":"Rona S Carroll","orcid":null,"position":5,"is_corresponding":false},{"id":72165,"name":"Min Chen","orcid":"0000-0001-5320-5729","position":6,"is_corresponding":false},{"id":160508,"name":"Lee S Weinstein","orcid":null,"position":7,"is_corresponding":false},{"id":160509,"name":"Stefan Offermanns","orcid":null,"position":8,"is_corresponding":false},{"id":160510,"name":"Ulrich Boehm","orcid":null,"position":9,"is_corresponding":false},{"id":160511,"name":"Daniel J Bernard","orcid":null,"position":10,"is_corresponding":false},{"id":160512,"name":"Ursula B Kaiser","orcid":"0000-0002-8237-0704","position":11,"is_corresponding":false},{"id":153061,"name":"George A. Stamatiades","orcid":"0000-0002-9407-6326","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":2.5649493574615367,"endowment":2.5649493574615367,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"34864945","pmcid":"PMC8711759","openalex_id":"https://openalex.org/W4200277703","authors":[],"funders":[{"funder_name":"National Institutes of Health","grant_id":"R37 HD019938","title":null},{"funder_name":"National Institutes of Health","grant_id":"R01 HD082314","title":null},{"funder_name":"National Institutes of Health","grant_id":"T32 DK007529","title":null},{"funder_name":"Canadian Institutes of Health Research","grant_id":"MOP-123447","title":null},{"funder_name":"Canadian Institutes of Health Research","grant_id":"PJT-169184","title":null},{"funder_name":"Canadian Institutes of Health Research","grant_id":"unidentified","title":"unidentified"}],"total_grants":6,"fwci":1.1558,"citation_percentile":0.7934121,"influential_citations":0,"citation_trend":[{"year":2022,"count":1},{"year":2023,"count":4},{"year":2024,"count":1},{"year":2025,"count":5},{"year":2026,"count":1}],"oa_status":"bronze","license":"OUP Standard Publication Reuse","oa_locations":[{"url":"https://academic.oup.com/endo/article-pdf/163/2/bqab247/41939211/bqab247.pdf","host_type":"journal"},{"url":"https://academic.oup.com/endo/article-pdf/163/2/bqab247/41939211/bqab247.pdf","host_type":"BRONZE"},{"url":"https://academic.oup.com/endo/article-pdf/163/2/bqab247/41939211/bqab247.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1210/endocr/bqab247","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/34864945","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/8711759","host_type":"repository"}],"fields_of_study":["Hypothalamic control of reproductive hormones","Ovarian function and disorders","Reproductive Biology and Fertility","Medicine","Biology","0402 animal and dairy science","04 agricultural and veterinary sciences","03 medical and health sciences","0302 clinical medicine","Animals","Castration","Cell Line","Chromogranins","Female","Fertility","Follicle Stimulating Hormone, beta Subunit","GTP-Binding Protein alpha Subunits, Gq-G11","GTP-Binding Protein alpha Subunits, Gs","Gene Expression Regulation","Gonadotrophs","Gonadotropin-Releasing Hormone","Gonadotropins","HEK293 Cells","Humans","Luteinizing Hormone","Male","Mice","Mice, Inbred C57BL","Mice, Knockout","Receptors, LHRH","Sexual Maturation","Signal Transduction"],"mesh_terms":["Animals","Castration","Cell Line","Chromogranins","Female","Fertility","Gene Expression Regulation","Gonadotropins","Humans","Luteinizing Hormone","Gonadotropin-Releasing Hormone","Male","Mice, Inbred C57BL","Receptors, LHRH","Sexual Maturation","Signal Transduction","Mice, Knockout","GTP-Binding Protein alpha Subunits, Gs","Follicle Stimulating Hormone, beta Subunit","GTP-Binding Protein alpha Subunits, Gq-G11","Mice","Gonadotrophs","HEK293 Cells"],"keywords":["Gonadotropic cell","GNRHR","Endocrinology","Internal medicine","Gonadotropin-releasing hormone","Gonadotropin","Luteinizing hormone","Biology","Knockout mouse","Gene knockdown","Follicle-stimulating hormone","Hypogonadotropic hypogonadism","Receptor","Hormone","Cell culture","Genetics","Medicine","GnRH receptor","Gonadotropes","Gnrh Signaling","Male","Mice, Knockout","Gonadotrophs","Cell Line","Mice, Inbred C57BL","Mice","Fertility","HEK293 Cells","Gene Expression Regulation","Follicle Stimulating Hormone, beta Subunit","Chromogranins","GTP-Binding Protein alpha Subunits, Gs","Animals","GTP-Binding Protein alpha Subunits, Gq-G11","Humans","Female","Castration","Gonadotropins"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-08T22:13:45.777134Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}