{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T13:56:32Z","timestamp":1753883792481,"version":"3.41.2"},"reference-count":97,"publisher":"The Endocrine Society","issue":"3","license":[{"start":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T00:00:00Z","timestamp":1738713600000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32 HD041921","P50 HD044405","P50 HD102172","R25 GM083252","P51 OD011106"],"award-info":[{"award-number":["T32 HD041921","P50 HD044405","P50 HD102172","R25 GM083252","P51 OD011106"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Office of the Vice Chancellor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,2,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Estrogen receptor \u03b1 (ER\u03b1) in the ventromedial (VMN) and arcuate (ARC) nuclei of female rodent mediobasal hypothalami (MBHs) provides a crucial molecular gateway facilitating estradiol (E2) regulation of sexual behavior, reproductive neuroendocrinology, and metabolic function. In female nonhuman primates (NHPs) and women, however, its hypothalamic counterpart remains unknown.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>We hypothesized that knockdown (KD) of ER\u03b1 expression in the hypothalamic VMN and ARC of female marmosets would diminish sexual receptivity, while simultaneously disrupting gonadotropic and metabolic homeostasis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We ovariectomized (OVX) adult female marmosets of comparable age and weight, immediately replaced E2 at midcycle levels, and approximately 1 month later assigned monkeys to diet-induced obesity (DIO) within group (1) control, receiving scrambled short hairpin RNA (shRNA), or (2) ER\u03b1KD, receiving selective ER\u03b1 gene silencing shRNA. Magnetic resonance imaging\u2013guided neural surgery enabled hypothalamic infusion of viral vector shRNA and subsequent brain immunohistochemistry enabled observer-validated, NIS-elements computer software quantification of ER\u03b1 knockdown.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>ER\u03b1 expression was significantly diminished in the VMN and ARC, but not the preoptic area (POA), of ER\u03b1KD females coincident with elimination of timely female sexual responses, more than 80% loss of female receptivity, modestly elevated gonadotropin levels, hyperglycemia, and diminished calorie consumption. Density and intensity of ER\u03b1-expressing cells in the VMN correlated positively with female sexual receptivity and calorie consumption, negatively with timeliness of female sexual responses, and in the ARC, correlated negatively with calorie consumption.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>ER\u03b1 activation in the female NHP MBH is critically important for female sexual behavior and modestly contributes to gonadotropic and metabolic control.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/jendso\/bvaf012","type":"journal-article","created":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T10:30:46Z","timestamp":1738751446000},"source":"Crossref","is-referenced-by-count":0,"title":["Hypothalamic Estrogen Receptor \u03b1 Is Essential for Female Marmoset Sexual Behavior Without Protecting From Obesity"],"prefix":"10.1210","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8612-401X","authenticated-orcid":false,"given":"Marissa","family":"Kraynak","sequence":"first","affiliation":[{"name":"Wisconsin National Primate Research Center, University of Wisconsin\u2013Madison , Madison, WI 53715 ,","place":["USA"]},{"name":"Endocrinology-Reproductive Physiology Training Program, University of Wisconsin\u2013Madison , Madison, WI 53715 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2295-5102","authenticated-orcid":false,"given":"Molly M","family":"Willging","sequence":"additional","affiliation":[{"name":"Wisconsin National Primate Research Center, University of Wisconsin\u2013Madison , Madison, WI 53715 ,","place":["USA"]},{"name":"Endocrinology-Reproductive Physiology Training Program, University of Wisconsin\u2013Madison , Madison, WI 53715 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel J","family":"Uhlrich","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Wisconsin\u2013Madison , Madison, WI 53705 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert A","family":"Shapiro","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Wisconsin\u2013Madison , Madison, WI 53705 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5089-5410","authenticated-orcid":false,"given":"Matthew T","family":"Flowers","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Wisconsin\u2013Madison , Madison, WI 53705 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen A","family":"Manning","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University of Wisconsin\u2013Madison , Madison, WI 53705 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara D","family":"John","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of Wisconsin\u2013Madison , Madison, WI 53705 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samantha M","family":"Williams","sequence":"additional","affiliation":[{"name":"Wisconsin National Primate Research Center, University of Wisconsin\u2013Madison , Madison, WI 53715 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lukas J","family":"Henjum","sequence":"additional","affiliation":[{"name":"Wisconsin National Primate Research Center, University of Wisconsin\u2013Madison , Madison, WI 53715 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca C","family":"Marrah","sequence":"additional","affiliation":[{"name":"Wisconsin National Primate Research Center, University of Wisconsin\u2013Madison , Madison, WI 53715 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hannah R","family":"Yohnk","sequence":"additional","affiliation":[{"name":"Wisconsin National Primate Research Center, University of Wisconsin\u2013Madison , Madison, WI 53715 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carter B","family":"Berg","sequence":"additional","affiliation":[{"name":"Wisconsin National Primate Research Center, University of Wisconsin\u2013Madison , Madison, WI 53715 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin","family":"Brunner","sequence":"additional","affiliation":[{"name":"Wisconsin National Primate Research Center, University of Wisconsin\u2013Madison , Madison, WI 53715 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