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Simultaneous hypophyseal portal and jugular blood samples were collected over 36 hr: 0\u201312 hr, in the presence of exogenous P (P treatment begun 8 days earlier); 12\u201324 hr, P implant removed; 24\u201336 hr, P implant reinserted. P removal caused a significant rapid increase in the GnRH pulse frequency, which was detectable within two pulses (175 min). P insertion suppressed the GnRH pulse frequency even faster: the effect detectable within one pulse (49 min). LH pulsatility was modulated identically. The next two experiments demonstrated that these effects of P are mediated by the nuclear P receptor since intracerebroventricularly infused P suppressed LH release but 3\u03b1-hydroxy-5\u03b1-pregnan-20-one, which operates through the type A \u03b3-aminobutyric acid receptor, was without effect and pretreatment with the P-receptor antagonist RU486 blocked the ability of P to inhibit LH. Our final study showed that P exerts its acute suppression of GnRH through an E-dependent system because the effects of P on LH secretion, lost after long-term E deprivation, are restored after 2 weeks of E treatment. Thus we demonstrate that P acutely inhibits GnRH through an E-dependent nuclear P-receptor system.<\/jats:p>","DOI":"10.1073\/pnas.95.18.10978","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:40:11Z","timestamp":1027680011000},"page":"10978-10983","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":143,"title":["The negative feedback actions of progesterone on gonadotropinreleasing hormone secretion are transduced by the classical progesterone receptor"],"prefix":"10.1073","volume":"95","author":[{"given":"Donal C.","family":"Skinner","sequence":"first","affiliation":[{"name":"Institut National de la Recherche Agronomique, Neuroendocrinologie Sexuelle, Physiologie de la Reproduction des Mammif\u00e9res Domestiques, Nouzilly 37380, France; Department of Veterinary Preclinical Studies, University of Glasgow Veterinary School, Bearsden Road, Glasgow, United Kingdom; Department of Physiology and Biophysics, West Virginia University, Morgantown, WV; and Service d\u2019Endocrinologie and Institut Federatif de Recherches, H\u00f4pital Saint Antoine, Assistance Publique, H\u00f4pitaux de Paris,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil P.","family":"Evans","sequence":"additional","affiliation":[{"name":"Institut National de la Recherche Agronomique, Neuroendocrinologie Sexuelle, Physiologie de la Reproduction des Mammif\u00e9res Domestiques, Nouzilly 37380, France; Department of Veterinary Preclinical Studies, University of Glasgow Veterinary School, Bearsden Road, Glasgow, United Kingdom; Department of Physiology and Biophysics, West Virginia University, Morgantown, WV; and Service d\u2019Endocrinologie and Institut Federatif de Recherches, H\u00f4pital Saint Antoine, Assistance Publique, H\u00f4pitaux de Paris,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernadette","family":"Delaleu","sequence":"additional","affiliation":[{"name":"Institut National de la Recherche Agronomique, Neuroendocrinologie Sexuelle, Physiologie de la Reproduction des Mammif\u00e9res Domestiques, Nouzilly 37380, France; Department of Veterinary Preclinical Studies, University of Glasgow Veterinary School, Bearsden Road, Glasgow, United Kingdom; Department of Physiology and Biophysics, West Virginia University, Morgantown, WV; and Service d\u2019Endocrinologie and Institut Federatif de Recherches, H\u00f4pital Saint Antoine, Assistance Publique, H\u00f4pitaux de Paris,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert L.","family":"Goodman","sequence":"additional","affiliation":[{"name":"Institut National de la Recherche Agronomique, Neuroendocrinologie Sexuelle, Physiologie de la Reproduction des Mammif\u00e9res Domestiques, Nouzilly 37380, France; Department of Veterinary Preclinical Studies, University of Glasgow Veterinary School, Bearsden Road, Glasgow, United Kingdom; Department of Physiology and Biophysics, West Virginia University, Morgantown, WV; and Service d\u2019Endocrinologie and Institut Federatif de Recherches, H\u00f4pital Saint Antoine, Assistance Publique, H\u00f4pitaux de Paris,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Bouchard","sequence":"additional","affiliation":[{"name":"Institut National de la Recherche Agronomique, Neuroendocrinologie Sexuelle, Physiologie de la Reproduction des Mammif\u00e9res Domestiques, Nouzilly 37380, France; 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