{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T06:04:31Z","timestamp":1780985071799,"version":"3.54.1"},"reference-count":65,"publisher":"The Endocrine Society","issue":"5","license":[{"start":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T00:00:00Z","timestamp":1773100800000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["1K08HD107134-01A1"],"award-info":[{"award-number":["1K08HD107134-01A1"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["T32ES007026"],"award-info":[{"award-number":["T32ES007026"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Polycystic ovary syndrome (PCOS) is a systemic endocrine disorder characterized by perturbations in both androgen and insulin signaling pathways that result in anovulatory infertility and metabolic syndrome. This study aimed to elucidate insulin signaling in the PCOS ovary using a mouse model that develops both the metabolic and reproductive manifestations of PCOS due to chronic postnatal dihydrotestosterone exposure. PCOS mice developed anovulation, cystic follicles, systemic insulin resistance with compensatory hyperinsulinemia and mild excess adiposity, but not hepatic steatosis, adipose inflammation or frank obesity, suggesting that hyperandrogenism is the main driver of the metabolic perturbations in this model. Insulin signaling was then assessed in the ovary, liver, and skeletal muscle from hyperinsulinemic, fasting PCOS mice. Ovarian theca and granulosa cells showed upregulated markers of insulin signaling, while the liver and skeletal muscle from the same mice showed no changes compared to controls. However, cultured primary PCOS hepatocytes were profoundly insulin resistant in vitro, while primary theca cells (TCs) and granulosa cells (GCs) isolated from the same PCOS mice were insulin sensitive. Both PCOS TCs and GCs produced significantly more steroid hormones than control cells when stimulated with insulin and gonadotropins. Our findings indicate that the PCOS ovary remains sensitive to insulin despite systemic insulin resistance and that insulin works synergistically with gonadotropins to stimulate ovarian testosterone production in PCOS. We therefore suggest that insulin resistance is not merely a byproduct of hyperandrogenism but is a disease-driving factor in PCOS and should be treated as a clinical target in PCOS management.<\/jats:p>","DOI":"10.1210\/endocr\/bqag025","type":"journal-article","created":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T12:38:17Z","timestamp":1772800697000},"source":"Crossref","is-referenced-by-count":2,"title":["Ovarian insulin signaling is intact despite systemic insulin resistance in a mouse model of polycystic ovary syndrome"],"prefix":"10.1210","volume":"167","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3971-5073","authenticated-orcid":false,"given":"Adelaide E","family":"Weidner","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Endocrinology, University of Rochester Medical Center, Rochester, NY 14642 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Rochester Medical Center, Rochester, NY 14642 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4035-4105","authenticated-orcid":false,"given":"Anna","family":"Roy","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology, University of Rochester Medical Center, Rochester, NY 14642 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0105-9464","authenticated-orcid":false,"given":"Zachary R","family":"Sechrist","sequence":"additional","affiliation":[{"name":"Center for Musculoskeletal Research, University of Rochester Medical Center , Rochester, NY 14642 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7365-9506","authenticated-orcid":false,"given":"Calvin L","family":"Cole","sequence":"additional","affiliation":[{"name":"Center for Musculoskeletal Research, 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