{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T01:50:21Z","timestamp":1789091421061,"version":"build-2803163510"},"reference-count":61,"publisher":"The Endocrine Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Alterations in androgen levels lead to reproductive defects in both males and females, including hypogonadotropic hypogonadism, anovulation, and infertility. Androgens have been shown to down-regulate GnRH mRNA levels through an androgen receptor (AR)-dependent mechanism. Here, we investigate how androgen regulates expression from the GnRH regulatory region in the GT1-7 cell line, a model of GnRH neurons. A synthetic androgen, R1881, repressed transcription from the GnRH promoter (GnRH-P) in an AR-dependent manner, and liganded AR associated with the chromatin at the GnRH-P in live GT1-7 cells. The three known octamer-binding transcription factor-1 (Oct-1) binding sites in GnRH-P were required for AR-mediated repression, although other sequences were also involved. Although a multimer of the consensus Oct-1 binding site was not repressed, a multimer of the cluster of Oct-1, Pre-B cell leukemia transcription factor (Pbx)\/Prep, and NK2 homeobox 1 (Nkx2.1) binding sites, found at \u2212106\/\u221291 in GnRH-P, was sufficient for repression. In fact, overexpression of any of these factors disrupted the androgen response, indicating that a balance of factors in this tripartite complex is required for AR repression. AR bound to this region in EMSA, indicating a direct interaction of AR with DNA or with other transcription factors bound to GnRH-P at this sequence. Collectively, our data demonstrate that GnRH transcription is repressed by AR via multiple sequences in GnRH-P, including three Oct-1 binding sites, and that this repression requires the complex interaction of several transcription factors.<\/jats:p>","DOI":"10.1210\/me.2011-1015","type":"journal-article","created":{"date-parts":[[2011,11,11]],"date-time":"2011-11-11T05:08:04Z","timestamp":1320988084000},"page":"2-13","source":"Crossref","is-referenced-by-count":18,"title":["Androgen Receptor Repression of GnRH Gene Transcription"],"prefix":"10.1210","volume":"26","author":[{"given":"Melissa J.","family":"Brayman","sequence":"first","affiliation":[{"name":"Department of Reproductive Medicine and The Center for Reproductive Science and Medicine, University of California, San Diego, La Jolla, California 92093-0674"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia A.","family":"Pepa","sequence":"additional","affiliation":[{"name":"Department of Reproductive Medicine and The Center for Reproductive Science and Medicine, University of California, San Diego, La Jolla, California 92093-0674"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara E.","family":"Berdy","sequence":"additional","affiliation":[{"name":"Department of Reproductive Medicine and The Center for Reproductive Science and Medicine, University of California, San Diego, La Jolla, California 92093-0674"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela L.","family":"Mellon","sequence":"additional","affiliation":[{"name":"Department of Reproductive Medicine and The Center for Reproductive Science and Medicine, University of California, San Diego, La Jolla, California 92093-0674"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071613504634600_B1","doi-asserted-by":"crossref","first-page":"3506","DOI":"10.1210\/endo.141.9.7788","article-title":"Detection of estrogen receptor-\u03b2 messenger 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