Monkey embryos were exposed to RU 486 both in vitro and in vivo (with and without progesterone therapy) in the perinidatory interval. These primate embryos were highly tolerant of RU 486, except when RU 486 alone terminated early pregnancy. There were no indications of teratogenicity in this limited trial when the embryos were exposed to RU 486 either before implantation (10-7M in 24-hour cultures) or during the immediate post-implantation interval (50 mg orally/day; days 32 to 39 LMP).

That the antiprogestin RU 486 delays or inhibits the LH surge, and induces premature luteolysis in monkeys and women concurrent with a reduction in LH/FSH secretion has been reported. Whether this inhibition of gonadotropin release was a result of action at the hypothalamic and/or pituitary level is unknown. Here, we utilized a rat pituitary cell culture system to evaluate direct RU 486 actions on pituitary gonadotropin secretion in vitro. Cell cultures were primed with 10 nM estradiol for 48 h in order to maintain progesterone receptors. Basal and GnRH-induced secretion were evaluated after a 4-hour incubation period. The progesterone antagonist RU 486 inhibited GnRH-induced LH and FSH secretion in a dose-dependent manner, without affecting basal gonadotropin release. This inhibition of gonadotropin secretion was specific and antagonized by addition of progesterone in vitro.

The noncompetitive antiestrogenic effects of RU 486 were examined using estradiol (E2)-treated ovariectomized monkeys given RU 486, progesterone (P), or both. The E2-induced luteinizing-hormone (LH) surge of control animals was abrogated by P and/or RU 486. Secretory transformation by P was inhibited by RU 486 coadministration. RU 486 alone (1 mg/kg) induced endometrial secretory transformation, but higher doses (5 mg/kg) inhibited proliferation and secretory activity. Thus in the presence of P, RU 486 is antagonistic but, in absence of P, exhibits endometrial progestational effects at low doses and an antiproliferative (antiestrogenic) effect at higher doses. These data encourage continued evaluation of RU 486 as a potential contraceptive agent acting at the pituitary and/or endometrial level.

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEstradiol binding of exceptionally high affinity by a nonhistone chromatin protein fractionAudrey Alberga, Nelly Massol, Jean P. Raynaud, and Etienne E. BaulieuCite this: Biochemistry 1971, 10, 21, 3835–3843Publication Date (Print):October 12, 1971Publication History Published online1 May 2002Published inissue 12 October 1971https://doi.org/10.1021/bi00797a006RIGHTS & PERMISSIONSArticle Views16Altmetric-Citations46LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (1 MB) Get e-Alerts Get e-Alerts

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStudies on Δ5→4-3-oxo steroid isomerases. I. Extraction model for enzymic activityFrancoise. Falcoz-Kelly, Etienne E. Baulieu, and Annette. AlfsenCite this: Biochemistry 1968, 7, 11, 4119–4125Publication Date (Print):November 1, 1968Publication History Published online1 May 2002Published inissue 1 November 1968https://doi.org/10.1021/bi00851a047RIGHTS & PERMISSIONSArticle Views33Altmetric-Citations18LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (606 KB) Get e-Alerts Get e-Alerts