title: Ulipristal blocks ovulation by inhibiting progesterone receptor-dependent pathways intrinsic to the ovary.
abstract: Ulipristal acetate (UPA), a progesterone receptor (PR) modulator, is used as an emergency contraceptive in women. Here, using a mouse model, we investigated the mechanism of action of UPA as an ovulation blocker. In mice, ovulation is induced ~12 hours following the treatment with exogenous gonadotropins, including human chorionic gonadotropin (hCG), which mimics the action of luteinizing hormone (LH). When administered within 6 hours of hCG treatment, UPA is a potent blocker of ovulation. However, UPA's effectiveness declined significantly when it was given at 8 hours post hCG. Our study revealed that, when administered within 6 hours of hCG, UPA blocks ovulation by inhibiting PR-dependent pathways intrinsic to the ovary. At 8 hours post hCG, when the PR signaling has already occurred, UPA is unable to block ovulation efficiently. Collectively, these results indicated that UPA, when administered within a critical time window following the LH surge, blocks PR-dependent pathways in the ovary to function as an effective antiovulatory contraceptive.
authors.affiliation: Department of Comparative Biosciences, University of Illinois Urbana/Champaign, Urbana, IL 61802, USA.
authors.forename: Shanmugasundaram
authors.initials: S
authors.lastname: Nallasamy
authors.forename: Jaeyeon
authors.initials: J
authors.lastname: Kim
authors.forename: Regine
authors.initials: R
authors.lastname: Sitruk-Ware
authors.forename: Milan
authors.initials: M
authors.lastname: Bagchi
authors.forename: Indrani
authors.initials: I
authors.lastname: Bagchi
mesh_terms: D000818:Animals; D003270:Contraceptive Agents / Q000494:pharmacology*; D005260:Female; D006801:Humans; D051379:Mice; D009649:Norpregnadienes / Q000494:pharmacology*; D010053:Ovary / Q000187:drug effects* / Q000378:metabolism; D010060:Ovulation / Q000187:drug effects* / Q000378:metabolism; D011980:Receptors, Progesterone / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology
chemical_list: D003270:Contraceptive Agents; D009649:Norpregnadienes; D011980:Receptors, Progesterone; C555622:ulipristal acetate