{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T07:23:28Z","timestamp":1790839408010,"version":"4.1.0"},"reference-count":47,"publisher":"The Endocrine Society","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,10,1]]},"abstract":"<jats:p>We previously identified FOXL2 as a critical component in FSH\u03b2 gene transcription. Here, we show that mice deficient in FOXL2 have lower levels of gonadotropin gene expression and fewer LH- and FSH-containing cells, but the same level of other pituitary hormones compared to wild-type littermates, highlighting a role of FOXL2 in the pituitary gonadotrope. Further, we investigate the function of FOXL2 in the gonadotrope cell and determine which domains of the FOXL2 protein are necessary for induction of FSH\u03b2 transcription. There is a stronger induction of FSH\u03b2 reporter transcription by truncated FOXL2 proteins, but no induction with the mutant lacking the forkhead domain. Specifically, FOXL2 plays a role in activin induction of FSH\u03b2, functioning in concert with activin-induced SMAD proteins. Activin acts through multiple promoter elements to induce FSH\u03b2 expression, some of which bind FOXL2. Each of these FOXL2-binding sites is either juxtaposed or overlapping with a SMAD-binding element. We determined that FOXL2 and SMAD4 proteins form a higher order complex on the most proximal FOXL2 site. Surprisingly, two other sites important for activin induction bind neither SMADs nor FOXL2, suggesting additional factors at work. Furthermore, we show that FOXL2 plays a role in synergistic induction of FSH\u03b2 by GnRH and activin through interactions with the cJUN component of the AP1 complex that is necessary for GnRH responsiveness. Collectively, our results demonstrate the necessity of FOXL2 for proper FSH production in mice and implicate FOXL2 in integration of transcription factors at the level of the FSH\u03b2 promoter.<\/jats:p>","DOI":"10.1210\/me.2014-1008","type":"journal-article","created":{"date-parts":[[2014,8,8]],"date-time":"2014-08-08T17:21:27Z","timestamp":1407518487000},"page":"1640-1655","source":"Crossref","is-referenced-by-count":23,"title":["Roles of Binding Elements, FOXL2 Domains, and Interactions With cJUN and SMADs in Regulation of FSH\u03b2"],"prefix":"10.1210","volume":"28","author":[{"given":"Lacey L.","family":"Roybal","sequence":"first","affiliation":[{"name":"Department of Reproductive Medicine (L.L.R., A.H., J.D.M., P.A.P., K.M.B., P.L.M., D.C.), Center for Reproductive Science and Medicine, University of California, San Diego, La Jolla, California 92093\u20130674;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arpi","family":"Hambarchyan","sequence":"additional","affiliation":[{"name":"Department of Reproductive Medicine (L.L.R., A.H., J.D.M., P.A.P., K.M.B., P.L.M., D.C.), Center for Reproductive Science and Medicine, University of California, San Diego, La Jolla, California 92093\u20130674;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason D.","family":"Meadows","sequence":"additional","affiliation":[{"name":"Department of Reproductive Medicine (L.L.R., A.H., J.D.M., P.A.P., K.M.B., P.L.M., D.C.), Center for Reproductive Science and Medicine, University of California, San Diego, La Jolla, California 92093\u20130674;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nermeen H.","family":"Barakat","sequence":"additional","affiliation":[{"name":"Division of Biomedical Sciences (N.H.B., D.C.), School of Medicine, University of California, Riverside; Riverside, California 92521"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia A.","family":"Pepa","sequence":"additional","affiliation":[{"name":"Department of Reproductive Medicine (L.L.R., A.H., J.D.M., P.A.P., K.M.B., P.L.M., D.C.), Center for Reproductive Science and Medicine, University of California, San Diego, La Jolla, California 92093\u20130674;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kellie M.","family":"Breen","sequence":"additional","affiliation":[{"name":"Department of Reproductive Medicine (L.L.R., A.H., J.D.M., P.A.P., K.M.B., P.L.M., D.C.), Center for Reproductive Science and Medicine, University of California, San Diego, La Jolla, California 92093\u20130674;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela L.","family":"Mellon","sequence":"additional","affiliation":[{"name":"Department of Reproductive Medicine (L.L.R., A.H., J.D.M., P.A.P., K.M.B., P.L.M., D.C.), Center for Reproductive Science and Medicine, University 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