{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T17:12:26Z","timestamp":1790356346863,"version":"4.1.0"},"reference-count":59,"publisher":"The Endocrine Society","issue":"5","license":[{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"NIH Research","award":["U54 AG062322"],"award-info":[{"award-number":["U54 AG062322"]}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000124","name":"Office of Research on Women's Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000124","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012264","name":"NIH","doi-asserted-by":"publisher","award":["HD090151"],"award-info":[{"award-number":["HD090151"]}],"id":[{"id":"10.13039\/501100012264","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012264","name":"NIH","doi-asserted-by":"publisher","award":["HD099084"],"award-info":[{"award-number":["HD099084"]}],"id":[{"id":"10.13039\/501100012264","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012264","name":"NIH","doi-asserted-by":"publisher","award":["DK133760"],"award-info":[{"award-number":["DK133760"]}],"id":[{"id":"10.13039\/501100012264","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>The preovulatory luteinizing hormone (LH) surge is a defining neuroendocrine event that triggers ovulation through estradiol (E2)-dependent positive feedback on gonadotropin-releasing hormone (GnRH) secretion. Mechanistic studies of this process have relied predominantly on ovariectomized rodents supplemented with exogenous hormones, a paradigm that disrupts ovarian function and limits physiological and translational relevance. Here, we establish a robust and reproducible model of LH surge induction in intact female mice that preserves the hypothalamic\u2013pituitary\u2013gonadal axis. We show that a single low-dose injection of estradiol benzoate (EB; 0.5\u2005\u00b5g) administered during diestrus reliably induces a temporally synchronized LH surge in most intact females, whereas EB treatment during proestrus or estrus is ineffective. EB-induced LH surges were accompanied by a significant increase in circulating progesterone, confirming the engagement of ovarian luteinizing pathways. The LH surge occurrence was independent of proestrus detection by vaginal cytology, accentuating the limited predictive value of cytology in mice. At the neuroendocrine level, EB treatment markedly increased cFOS expression in GnRH neurons across key preoptic regions and modestly activated kisspeptin neurons in the rostral periventricular area of the third ventricle, consistent with activation of E2-positive feedback circuitry. In contrast, arcuate kisspeptin neurons remained inactive, supporting their role in negative feedback. Together, these findings define a physiologically relevant, intact mouse model for studying E2-induced LH surges that maintains endogenous ovarian signaling.<\/jats:p>","DOI":"10.1210\/endocr\/bqag042","type":"journal-article","created":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T11:31:21Z","timestamp":1776166281000},"source":"Crossref","is-referenced-by-count":1,"title":["A protocol for physiologic LH surge induction in gonad intact female mice"],"prefix":"10.1210","volume":"167","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4447-6388","authenticated-orcid":false,"given":"Mauro S B","family":"Silva","sequence":"first","affiliation":[{"name":"Mass General Brigham, Department of Medicine, Endocrine Division , Boston, MA 02115, USA"},{"name":"Harvard Medical School , Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajae","family":"Talbi","sequence":"additional","affiliation":[{"name":"Mass General Brigham, Department of Medicine, Endocrine Division , Boston, MA 02115, USA"},{"name":"Harvard Medical School , Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Encarnaci\u00f3n","family":"Torres","sequence":"additional","affiliation":[{"name":"Mass General Brigham, Department of Medicine, Endocrine Division , Boston, MA 02115, USA"},{"name":"Harvard Medical School , Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Zdon","sequence":"additional","affiliation":[{"name":"Mass General Brigham, Department of Medicine, Endocrine Division , Boston, MA 02115, USA"},{"name":"Harvard Medical School , Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sidney A","family":"Pereira","sequence":"additional","affiliation":[{"name":"Mass General Brigham, Department of Medicine, Endocrine Division , Boston, MA 02115, USA"},{"name":"Harvard Medical School , Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George A","family":"Stamatiades","sequence":"additional","affiliation":[{"name":"Mass General Brigham, Department of Medicine, Endocrine Division , Boston, MA 02115, USA"},{"name":"Harvard Medical School , Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Lopez","sequence":"additional","affiliation":[{"name":"Mass General Brigham, Department of Medicine, Endocrine Division , Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rona S","family":"Carroll","sequence":"additional","affiliation":[{"name":"Mass General Brigham, Department of Medicine, Endocrine Division , Boston, MA 02115, USA"},{"name":"Harvard Medical School , Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5799-219X","authenticated-orcid":false,"given":"V\u00edctor M","family":"Navarro","sequence":"additional","affiliation":[{"name":"Mass General Brigham, Department of Medicine, Endocrine Division , Boston, MA 02115, USA"},{"name":"Harvard Medical School , Boston, MA 02115, USA"},{"name":"Harvard Program in Neuroscience , Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2026,4,16]]},"reference":[{"issue":"3","key":"2026050522162310700_bqag042-B1","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1210\/endo-129-3-1175","article-title":"Pattern of gonadotropin-releasing hormone (GnRH) secretion leading up to ovulation in the ewe: existence of a preovulatory GnRH surge","volume":"129","author":"Moenter","year":"1991","journal-title":"Endocrinology"},{"issue":"2","key":"2026050522162310700_bqag042-B2","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1095\/biolreprod56.2.303","article-title":"Gonadotropin-releasing hormone requirements for 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