{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:53:14Z","timestamp":1792799594646,"version":"4.5.0"},"reference-count":72,"publisher":"American Society for Clinical Investigation","issue":"17","funder":[{"name":"NIH","award":["R00-HD068130"],"award-info":[{"award-number":["R00-HD068130"]}]},{"name":"NICHD","award":["5R01HD095512"],"award-info":[{"award-number":["5R01HD095512"]}],"id":[{"id":"https:\/\/ror.org\/04byxyr05","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,9,5]]},"abstract":"<jats:p>\n                    Many women with hyperandrogenemia suffer from irregular menses and infertility. However, it is unknown whether androgens directly affect reproduction. Since animal models of hyperandrogenemia-induced infertility are associated with obesity, which may impact reproductive function, we have created a lean mouse model of elevated androgen levels using implantation of low-dose 5\u03b1-dihydrotestosterone (DHT) pellets to separate the effects of elevated androgen levels from obesity. The hypothalamic-pituitary-gonadal axis controls reproduction. While we have demonstrated that androgens impair ovarian function, androgens could also disrupt neuroendocrine function at the level of brain and\/or pituitary to cause infertility. To understand how elevated androgen levels might act on pituitary gonadotropes to influence reproductive function, female mice with disruption of the androgen receptor (\n                    <jats:italic>Ar<\/jats:italic>\n                    ) gene specifically in pituitary gonadotropes (PitARKO) were produced. DHT-treated control mice with intact pituitary\n                    <jats:italic>Ar<\/jats:italic>\n                    (Con-DHT) exhibited disrupted estrous cyclicity and fertility with reduced pituitary responsiveness to gonadotropin-releasing hormone (GnRH) at the level of both calcium signaling and luteinizing hormone (LH) secretion. These effects were ameliorated in DHT-treated PitARKO mice. Calcium signaling controls GnRH regulation of LH vesicle exotocysis. Our data implicate upregulation of GEM (a voltage-dependent calcium channel inhibitor) in the pituitary as a potential mechanism for the pathological effects of androgens. These results demonstrate that gonadotrope AR, as an extraovarian regulator, plays an important role in reproductive pathophysiology.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.127817","type":"journal-article","created":{"date-parts":[[2019,8,8]],"date-time":"2019-08-08T12:01:58Z","timestamp":1565265718000},"source":"Crossref","is-referenced-by-count":20,"title":["Gonadotrope androgen receptor mediates pituitary responsiveness to hormones and androgen-induced subfertility"],"prefix":"10.1172","volume":"4","author":[{"given":"Zhiqiang","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingxiao","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, 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