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Although Hippo kinase cascade activity was recently reported in the anterior pituitary gland in mice, the role of the Hippo effectors in regulating gonadotropin production remains unknown. The objective of this study was therefore to characterize the roles of YAP and TAZ in gonadotropin synthesis and secretion. Using a conditional gene targeting approach (cKO), we found that gonadotrope-specific inactivation of Yap and Taz resulted in increased circulating levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in adult male mice, along with increased testosterone levels and testis weight. Female cKO mice had increased circulating LH (but not FSH) levels, which were associated with a hyperfertility phenotype characterized by higher ovulation rates and larger litter sizes. Unexpectedly, the loss of YAP\/TAZ did not appear to affect the expression of gonadotropin subunit genes, yet both basal and GnRH-induced LH secretion were increased in cultured pituitary cells from cKO mice. Likewise, pharmacologic inhibition of YAP binding to the TEAD family of transcription factors increased both basal and GnRH-induced LH secretion in L\u03b2T2 gonadotrope-like cells in vitro without affecting Lhb expression. Conversely, mRNA levels of ChgA and SgII, which encode key secretory granule cargo proteins, were decreased following pharmacologic inhibition of YAP\/TAZ, suggesting a mechanism whereby YAP\/TAZ regulate the LH secretion machinery in gonadotrope cells. Together, these findings represent the first evidence that Hippo signaling may play a role in regulating pituitary LH secretion.<\/jats:p>","DOI":"10.1210\/endocr\/bqab238","type":"journal-article","created":{"date-parts":[[2021,12,14]],"date-time":"2021-12-14T17:13:55Z","timestamp":1639502035000},"source":"Crossref","is-referenced-by-count":20,"title":["The Hippo Pathway Effectors YAP and TAZ Regulate LH Release by Pituitary Gonadotrope Cells in Mice"],"prefix":"10.1210","volume":"163","author":[{"given":"Ariane","family":"Lalonde-Larue","sequence":"first","affiliation":[{"name":"Centre de recherche en reproduction et fertilit\u00e9 (CRRF), Facult\u00e9 de m\u00e9decine V\u00e9t\u00e9rinaire, Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, Quebec J2S 7C6, 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reproduction et fertilit\u00e9 (CRRF), Facult\u00e9 de m\u00e9decine V\u00e9t\u00e9rinaire, Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, Quebec J2S 7C6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5365-5586","authenticated-orcid":false,"given":"Daniel J","family":"Bernard","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec H3G 1Y6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0089-9955","authenticated-orcid":false,"given":"Gustavo","family":"Zamberlam","sequence":"additional","affiliation":[{"name":"Centre de recherche en reproduction et fertilit\u00e9 (CRRF), Facult\u00e9 de m\u00e9decine V\u00e9t\u00e9rinaire, Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, Quebec J2S 7C6, 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