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Adult Suffolk ewes prenatally exposed to testosterone (T) display an array of reproductive and metabolic dysfunctions similar to those seen in women with polycystic ovarian syndrome (<jats:styled-content style=\"fixed-case\">PCOS<\/jats:styled-content>), including insulin resistance. Moreover, prenatal T treatment alters neuropeptide expression in <jats:styled-content style=\"fixed-case\">KND<\/jats:styled-content>y (co\u2010expressing kisspeptin, neurokinin B\/dynorphin) and agouti\u2010related peptide (Ag<jats:styled-content style=\"fixed-case\">RP<\/jats:styled-content>) neurons in the arcuate nucleus, two populations that play key roles in the control of reproduction and metabolism, respectively. In this study, we determined whether prenatal T treatment also altered insulin receptors in <jats:styled-content style=\"fixed-case\">KND<\/jats:styled-content>y and Ag<jats:styled-content style=\"fixed-case\">RP<\/jats:styled-content> neurons, as well as in preoptic area (<jats:styled-content style=\"fixed-case\">POA<\/jats:styled-content>) kisspeptin, pro\u2010opiomelanocortin (<jats:styled-content style=\"fixed-case\">POMC<\/jats:styled-content>), and gonadotropin\u2010releasing hormone (Gn<jats:styled-content style=\"fixed-case\">RH<\/jats:styled-content>) neurons of the adult sheep brain. Immunofluorescent detection of the beta subunit of insulin receptor (<jats:styled-content style=\"fixed-case\">IR<\/jats:styled-content>\u03b2) revealed that <jats:styled-content style=\"fixed-case\">KND<\/jats:styled-content>y, Ag<jats:styled-content style=\"fixed-case\">RP<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">POMC<\/jats:styled-content> neurons, but not Gn<jats:styled-content style=\"fixed-case\">RH<\/jats:styled-content> or <jats:styled-content style=\"fixed-case\">POA<\/jats:styled-content> kisspeptin neurons, colocalize <jats:styled-content style=\"fixed-case\">IR<\/jats:styled-content>\u03b2 in control females. Moreover, prenatal T treatment decreased the percentage of <jats:styled-content style=\"fixed-case\">KND<\/jats:styled-content>y and Ag<jats:styled-content style=\"fixed-case\">RP<\/jats:styled-content> neurons that colocalized <jats:styled-content style=\"fixed-case\">IR<\/jats:styled-content>\u03b2, consistent with reduced insulin sensitivity. Administration of the anti\u2010androgen drug, Flutamide, during prenatal T treatment, prevented the reduction in <jats:styled-content style=\"fixed-case\">IR<\/jats:styled-content>\u03b2 colocalization in Ag<jats:styled-content style=\"fixed-case\">RP<\/jats:styled-content>, but not in <jats:styled-content style=\"fixed-case\">KND<\/jats:styled-content>y neurons, suggesting that these effects are programmed by androgenic and oestrogenic actions, respectively. These findings provide novel insight into the effects of prenatal T treatment on hypothalamic insulin sensitivity and raise the possibility that decreased insulin receptors, specifically within <jats:styled-content style=\"fixed-case\">KND<\/jats:styled-content>y and Ag<jats:styled-content style=\"fixed-case\">RP<\/jats:styled-content> neurons, may contribute to the <jats:styled-content style=\"fixed-case\">PCOS<\/jats:styled-content>\u2010like phenotype of this animal model.<\/jats:p>","DOI":"10.1111\/ejn.13373","type":"journal-article","created":{"date-parts":[[2016,8,20]],"date-time":"2016-08-20T14:46:40Z","timestamp":1471704400000},"page":"2557-2568","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Prenatal testosterone exposure decreases colocalization of insulin receptors in kisspeptin\/neurokinin B\/dynorphin and agouti\u2010related peptide neurons of the adult ewe"],"prefix":"10.1111","volume":"44","author":[{"given":"Maria","family":"Cernea","sequence":"first","affiliation":[{"name":"Department of Neurobiology and Anatomical Sciences The University of Mississippi Medical Center Jackson MS 39232 USA"},{"name":"Department of Anatomy &amp; Cell Biology The University of Western Ontario London Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Phillips","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Anatomical Sciences The University of Mississippi Medical Center Jackson MS 39232 USA"},{"name":"Department of Anatomy &amp; Cell Biology The University of Western Ontario London Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasantha","family":"Padmanabhan","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Pediatrics, and Reproductive Sciences Program The University of Michigan Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lique M.","family":"Coolen","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics The University of Mississippi Medical Center Jackson MS USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael N.","family":"Lehman","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Anatomical Sciences The University of Mississippi Medical Center Jackson MS 39232 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,9,14]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-59745-108-6_6"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.19-17-07300.1999"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2011-2074"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1677\/joe.0.1520329"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo-108-4-1441"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2009-1190"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2004.02.127"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-20-09048.2002"},{"key":"e_1_2_7_10_1","first-page":"SUN\u2010701","article-title":"The effects of a Kisspeptin\u2010cell specific deletion of PI3K catalytic subunits p110\u03b1 and p110\u03b2 on the hypothalamic\u2010pituitary\u2010gonadal axis","volume":"33","author":"Beymer M.","year":"2012","journal-title":"Endocr. 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