{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T22:12:35Z","timestamp":1783548755102,"version":"3.55.0"},"reference-count":127,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,2,27]],"date-time":"2022-02-27T00:00:00Z","timestamp":1645920000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000052","name":"NIH Office of the Director","doi-asserted-by":"publisher","award":["R01 RR013635"],"award-info":[{"award-number":["R01 RR013635"]}],"id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000052","name":"NIH Office of the Director","doi-asserted-by":"publisher","award":["P51 OD011106"],"award-info":[{"award-number":["P51 OD011106"]}],"id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000071","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["P50 HD044405"],"award-info":[{"award-number":["P50 HD044405"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>As in women with polycystic ovary syndrome (PCOS), hyperinsulinemia is associated with anovulation in PCOS-like female rhesus monkeys. Insulin sensitizers ameliorate hyperinsulinemia and stimulate ovulatory menstrual cycles in PCOS-like monkeys. To determine whether hyperinsulinemia (&gt;694 pmol\/L), alone, induces PCOS-like traits, five PCOS-like female rhesus monkeys with minimal PCOS-like traits, and four control females of similar mid-to-late reproductive years and body mass index, received daily subcutaneous injections of recombinant human insulin or diluent for 6\u20137 months. A cross-over experimental design enabled use of the same monkeys in each treatment phase. Insulin treatment unexpectedly normalized follicular phase duration in PCOS-like, but not control, females. In response to an intramuscular injection of 200 IU hCG, neither prenatally androgenized nor control females demonstrated ovarian hyperandrogenic responses while receiving insulin. An intravenous GnRH (100 ng\/kg) injection also did not reveal evidence of hypergonadotropism. Taken together, these results suggest that experimentally induced adult hyperinsulinemia, alone, is insufficient to induce PCOS-like traits in female rhesus monkeys and to amplify intrinsic PCOS-like pathophysiology.<\/jats:p>","DOI":"10.3390\/ijms23052635","type":"journal-article","created":{"date-parts":[[2022,2,27]],"date-time":"2022-02-27T20:47:17Z","timestamp":1645994837000},"page":"2635","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Experimentally Induced Hyperinsulinemia Fails to Induce Polycystic Ovary Syndrome-like Traits in Female Rhesus Macaques"],"prefix":"10.3390","volume":"23","author":[{"given":"Rao","family":"Zhou","sequence":"first","affiliation":[{"name":"Wisconsin National Primate Research Center, University of Wisconsin, Madison, WI 53715, USA"},{"name":"Endocrinology Reproductive Physiology Training Program, University of Wisconsin, Madison, WI 53715, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristin M.","family":"Bruns","sequence":"additional","affiliation":[{"name":"Departments of Medicine, University of Wisconsin, Madison, WI 53715, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian M.","family":"Bird","sequence":"additional","affiliation":[{"name":"Endocrinology Reproductive Physiology Training Program, University of Wisconsin, Madison, WI 53715, USA"},{"name":"Departments of Obstetrics and Gynecology, University of Wisconsin, Madison, WI 53715, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph W.","family":"Kemnitz","sequence":"additional","affiliation":[{"name":"Wisconsin National Primate Research Center, University of Wisconsin, Madison, WI 53715, USA"},{"name":"Departments of Cell and Regenerative Biology, University of Wisconsin, Madison, WI 53715, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0387-1277","authenticated-orcid":false,"given":"Daniel A.","family":"Dumesic","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8249-263X","authenticated-orcid":false,"given":"David H.","family":"Abbott","sequence":"additional","affiliation":[{"name":"Wisconsin National Primate Research Center, University of Wisconsin, Madison, WI 53715, USA"},{"name":"Endocrinology Reproductive Physiology Training Program, University of Wisconsin, Madison, WI 53715, USA"},{"name":"Departments of Obstetrics and Gynecology, University of Wisconsin, Madison, WI 53715, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1056\/NEJM199509283331307","article-title":"Polycystic ovary syndrome","volume":"333","author":"Franks","year":"1995","journal-title":"N. 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