{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:56:10Z","timestamp":1790837770278,"version":"4.1.0"},"reference-count":66,"publisher":"The Endocrine Society","issue":"11","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Elman Poole Foundation"},{"DOI":"10.13039\/100014669","name":"British Society for Neuroendocrinology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014669","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001539","name":"Hope Foundation for Research on Ageing","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001539","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of Otago\u2019s Doctoral Scholarship"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Menopausal hormone therapy (MHT), prescribed for climacteric symptoms including hot flushes and weight gain, contains estrogens such as 17 beta-estradiol (17\u03b2E2). However, estrogen receptor activation by MHT may increase reproductive cancers in some people. As the protective metabolic effects of 17\u03b2E2 are partly mediated through the arcuate nucleus (ARC) of the hypothalamus, restricting 17\u03b2E2 actions to the brain could serve as a safer method for MHT. The prodrug 10\u03b2,17\u03b2-dihydroxyestra-1,4-dien-3-one (DHED) is enzymatically converted into 17\u03b2E2 exclusively within the brain. DHED has already demonstrated positive benefit in rodent models of hot flushes and cognitive decline, while avoiding peripheral hormonal burden. Therefore, we hypothesized that DHED treatment in obese female mice would act within the hypothalamus to provide the same beneficial metabolic effects as 17\u03b2E2. Female mice were ovariectomized, placed on a high fat diet and split into control, 17\u03b2E2, or DHED treatment groups. Body weight, uterine weight, glucose tolerance and peripheral concentrations of luteinizing hormone were recorded, along with the expression of the progesterone receptor and kisspeptin mRNA within the ARC. Delivery of DHED at a similar dose as 17\u03b2E2 failed to improve metabolic parameters or recapitulate the hypothalamic responses induced by 17\u03b2E2. Our findings subsequently show that delivery of DHED at higher doses elicited estrogen-like actions within the brain but still failed to improve metabolic health. Additional investigations surrounding DHED's conversion to 17\u03b2E2 within the hypothalamus are warranted to conclude whether estradiol actions exclusively within the central nervous system can independently regulate protective effects on metabolism.<\/jats:p>","DOI":"10.1210\/endocr\/bqag082","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T11:49:30Z","timestamp":1787226570000},"source":"Crossref","is-referenced-by-count":0,"title":["Targeting estrogen to the brain via DHED does not seem to protect against metabolic dysfunction in obese OVX mice"],"prefix":"10.1210","volume":"167","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-6707-5975","authenticated-orcid":false,"given":"Celine","family":"Camon","sequence":"first","affiliation":[{"name":"Centre for Neuroendocrinology, University of Otago , Dunedin 9016 ,","place":["New Zealand"]},{"name":"Department of Integrative Biology and Physiology, University of California Los Angeles , Los Angeles, CA 90095 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elodie","family":"Kip","sequence":"additional","affiliation":[{"name":"Centre for Neuroendocrinology, University of Otago , Dunedin 9016 ,","place":["New Zealand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Lord","sequence":"additional","affiliation":[{"name":"Centre for Neuroendocrinology, University of Otago , Dunedin 9016 ,","place":["New Zealand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Decourt","sequence":"additional","affiliation":[{"name":"Centre for Neuroendocrinology, University of Otago , Dunedin 9016 ,","place":["New Zealand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mel","family":"Prescott","sequence":"additional","affiliation":[{"name":"Centre for Neuroendocrinology, University of Otago , Dunedin 9016 ,","place":["New 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Veen","sequence":"additional","affiliation":[{"name":"Department of Integrative Biology and Physiology, University of California Los Angeles , Los Angeles, CA 90095 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katalin","family":"Prokai-Tatrai","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Neuroscience, University of North Texas Health Science Center , Fort Worth, TX 76107 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie M","family":"Correa","sequence":"additional","affiliation":[{"name":"Department of Integrative Biology and Physiology, University of California Los Angeles , Los Angeles, CA 90095 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0309-532X","authenticated-orcid":false,"given":"Rebecca E","family":"Campbell","sequence":"additional","affiliation":[{"name":"Centre for Neuroendocrinology, 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