{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T23:33:31Z","timestamp":1790984011074,"version":"4.1.0"},"reference-count":71,"publisher":"The Endocrine Society","issue":"3","license":[{"start":{"date-parts":[[2023,1,9]],"date-time":"2023-01-09T00:00:00Z","timestamp":1673222400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HD069702"],"award-info":[{"award-number":["R01HD069702"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HD096324"],"award-info":[{"award-number":["R01HD096324"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HD104345"],"award-info":[{"award-number":["R01HD104345"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32HD079342"],"award-info":[{"award-number":["T32HD079342"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01DK056731"],"award-info":[{"award-number":["R01DK056731"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01GM086596"],"award-info":[{"award-number":["R01GM086596"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["F31 HD102160"],"award-info":[{"award-number":["F31 HD102160"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of Virginia Center for Research in Reproduction"},{"name":"Ligand Assay and Analysis Core"},{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["R24 HD102061"],"award-info":[{"award-number":["R24 HD102061"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"name":"MMPC","award":["U2CDK110768"],"award-info":[{"award-number":["U2CDK110768"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,1,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Androgens are steroid hormones crucial for sexual differentiation of the brain and reproductive function. In excess, however, androgens may decrease fertility as observed in polycystic ovary syndrome, a common endocrine disorder characterized by oligo\/anovulation and\/or polycystic ovaries. Hyperandrogenism may also disrupt energy homeostasis, inducing higher central adiposity, insulin resistance, and glucose intolerance, which may exacerbate reproductive dysfunction. Androgens bind to androgen receptors (ARs), which are expressed in many reproductive and metabolic tissues, including brain sites that regulate the hypothalamo-pituitary-gonadal axis and energy homeostasis. The neuronal populations affected by androgen excess, however, have not been defined. We and others have shown that, in mice, AR is highly expressed in leptin receptor (LepRb) neurons, particularly in the arcuate (ARH) and the ventral premammillary nuclei (PMv). Here, we assessed if LepRb neurons, which are critical in the central regulation of energy homeostasis and exert permissive actions on puberty and fertility, have a role in the pathogenesis of female hyperandrogenism. Prenatally androgenized (PNA) mice lacking AR in LepRb cells (LepRb\u0394AR) show no changes in body mass, body composition, glucose homeostasis, or sexual maturation. They do show, however, a remarkable improvement of estrous cycles combined with normalization of ovary morphology compared to PNA controls. Our findings indicate that the prenatal androgenization effects on adult reproductive physiology (ie, anestrus and anovulation) are mediated by a subpopulation of LepRb neurons directly sensitive to androgens. They also suggest that the effects of hyperandrogenism on sexual maturation and reproductive function in adult females are controlled by distinct neural circuits.<\/jats:p>","DOI":"10.1210\/endocr\/bqad015","type":"journal-article","created":{"date-parts":[[2023,1,23]],"date-time":"2023-01-23T08:17:14Z","timestamp":1674461834000},"source":"Crossref","is-referenced-by-count":10,"title":["Deletion of Androgen Receptor in LepRb Cells Improves Estrous Cycles in Prenatally Androgenized Mice"],"prefix":"10.1210","volume":"164","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2140-2573","authenticated-orcid":false,"given":"Alexandra L","family":"Cara","sequence":"first","affiliation":[{"name":"Department of Molecular & Integrative Physiology, University of Michigan , Ann Arbor, Michigan 48109 , USA"},{"name":"Department of Integrative Biology and Physiology, University of California, Los Angeles , Los Angeles, California 90095 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9545-0287","authenticated-orcid":false,"given":"Laura L","family":"Burger","sequence":"additional","affiliation":[{"name":"Department of Molecular & Integrative Physiology, University of Michigan , Ann Arbor, Michigan 48109 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8422-0072","authenticated-orcid":false,"given":"Bethany G","family":"Beekly","sequence":"additional","affiliation":[{"name":"Department of Molecular & Integrative Physiology, University of Michigan , Ann Arbor, Michigan 48109 , USA"},{"name":"Neuroscience Graduate Program, University of Michigan , Ann Arbor, Michigan 48109 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8271-0115","authenticated-orcid":false,"given":"Susan J","family":"Allen","sequence":"additional","affiliation":[{"name":"Department of Molecular & Integrative Physiology, University of Michigan , Ann Arbor, Michigan 48109 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily L","family":"Henson","sequence":"additional","affiliation":[{"name":"Department of Molecular & Integrative Physiology, University of Michigan , Ann Arbor, Michigan 48109 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6815-6181","authenticated-orcid":false,"given":"Richard J","family":"Auchus","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Michigan , Ann Arbor, Michigan 48109 , USA"},{"name":"Department of Pharmacology, University of Michigan , Ann Arbor, Michigan 48109 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9468-2046","authenticated-orcid":false,"suffix":"Jr","given":"Martin G","family":"Myers","sequence":"additional","affiliation":[{"name":"Department of Molecular & Integrative Physiology, University of Michigan , Ann Arbor, Michigan 48109 , USA"},{"name":"Neuroscience Graduate Program, University of Michigan , Ann Arbor, Michigan 48109 , USA"},{"name":"Department of Internal Medicine, University of Michigan , Ann Arbor, Michigan 48109 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9812-0497","authenticated-orcid":false,"given":"Suzanne M","family":"Moenter","sequence":"additional","affiliation":[{"name":"Department of Molecular & Integrative Physiology, University of Michigan , Ann Arbor, Michigan 48109 , USA"},{"name":"Neuroscience Graduate Program, University of Michigan , Ann Arbor, Michigan 48109 , USA"},{"name":"Department of Internal Medicine, University of Michigan , Ann Arbor, Michigan 48109 , USA"},{"name":"Department of Obstetrics and Gynecology, University of Michigan , Ann Arbor, Michigan 48109 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9878-9203","authenticated-orcid":false,"given":"Carol F","family":"Elias","sequence":"additional","affiliation":[{"name":"Department of Molecular & Integrative Physiology, University of Michigan , Ann Arbor, Michigan 48109 , USA"},{"name":"Neuroscience Graduate Program, University of Michigan , Ann Arbor, Michigan 48109 , USA"},{"name":"Department of Obstetrics and Gynecology, University of Michigan , Ann Arbor, Michigan 48109 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2023,1,23]]},"reference":[{"issue":"1","key":"2023052322381657200_bqad015-B1","doi-asserted-by":"crossref","first-page":"16057","DOI":"10.1038\/nrdp.2016.57","article-title":"Polycystic ovary syndrome","volume":"2","author":"Azziz","year":"2016","journal-title":"Nat Rev Dis Primers"},{"issue":"1","key":"2023052322381657200_bqad015-B2","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.fertnstert.2016.05.003","article-title":"Criteria, prevalence, and phenotypes of polycystic ovary syndrome","volume":"106","author":"Lizneva","year":"2016","journal-title":"Fertil Steril"},{"issue":"1","key":"2023052322381657200_bqad015-B3","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1093\/humrep\/deh098","article-title":"Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS)","volume":"19","author":"Rotterdam ESHRE\/ASRM-Sponsored PCOS Consensus Workshop Group","year":"2004","journal-title":"Hum Reprod"},{"issue":"5","key":"2023052322381657200_bqad015-B4","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1210\/er.2015-1018","article-title":"Scientific statement on the diagnostic criteria, epidemiology, pathophysiology, and molecular genetics of polycystic ovary syndrome","volume":"36","author":"Dumesic","year":"2015","journal-title":"Endocr Rev"},{"issue":"3","key":"2023052322381657200_bqad015-B5","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1210\/jc.2013-3399","article-title":"Hyperandrogenemia predicts metabolic phenotype in polycystic ovary syndrome: the utility of serum androstenedione","volume":"99","author":"O\u2019Reilly","year":"2014","journal-title":"J Clin Endocrinol Metab"},{"issue":"4","key":"2023052322381657200_bqad015-B6","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1093\/humupd\/dml017","article-title":"The origins and sequelae of abnormal neuroendocrine function in polycystic ovary syndrome","volume":"12","author":"Blank","year":"2006","journal-title":"Hum Reprod Update"},{"issue":"2","key":"2023052322381657200_bqad015-B7","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1210\/en.2010-0823","article-title":"Prenatal androgenization of female mice programs an increase in firing activity of 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origins","volume":"29","author":"Walters","year":"2018","journal-title":"Trends Endocrinol Metab"},{"issue":"16","key":"2023052322381657200_bqad015-B16","doi-asserted-by":"crossref","first-page":"E3334","DOI":"10.1073\/pnas.1616467114","article-title":"Neuroendocrine androgen action is a key extraovarian mediator in the development of polycystic ovary syndrome","volume":"114","author":"Caldwell","year":"2017","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"5","key":"2023052322381657200_bqad015-B17","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1002\/cne.22025","article-title":"Leptin targets in the mouse brain","volume":"514","author":"Scott","year":"2009","journal-title":"J Comp Neurol"},{"issue":"4","key":"2023052322381657200_bqad015-B18","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1002\/(SICI)1096-9861(19980615)395:4<535::AID-CNE9>3.0.CO;2-2","article-title":"Distributions of leptin receptor mRNA isoforms in the rat 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Neuroendocrinol"},{"issue":"5","key":"2023052322381657200_bqad015-B40","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1369\/0022155417694870","article-title":"Tyramide signal amplification permits immunohistochemical analyses of androgen receptors in the rat prefrontal cortex","volume":"65","author":"Low","year":"2017","journal-title":"J Histochem Cytochem"},{"issue":"7","key":"2023052322381657200_bqad015-B41","doi-asserted-by":"crossref","first-page":"2827","DOI":"10.1210\/jc.2018-02485","article-title":"Exome sequencing reveals the POLR3H gene as a novel cause of primary ovarian insufficiency","volume":"104","author":"Franca","year":"2019","journal-title":"J Clin Endocrinol Metab"},{"key":"2023052322381657200_bqad015-B42","volume-title":"Paxinos and Franklin\u2019s The Mouse Brain in Stereotaxic Coordinates","author":"Paxinos","year":"2008","edition":"3rd 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