title: Progesterone antagonist RU 486 accommodates but does not induce labour and delivery in primates.
abstract: The hormonal mechanisms of parturition in primates remain controversial. Even so, the well-known decrease of plasma progesterone concentration near term is considered by many as the 'labour inducer'. The progesterone antagonist RU 486, which blocks progesterone activity at the cellular receptor level, appears to be a useful hormonal tool by which to study this tissue. Here, we tested its capacity to induce labour and delivery. A total of 23 Cynomolgus monkeys (Macaca fascicularis), within 9-17 days of expected term, were assigned to four different protocols to study various doses, routes and regimens of RU 486 administration. Observations included uterine contractile patterns, pharmacokinetics of RU 486 in plasma and passage of RU 486 into breast milk. None of the protocols tested successfully induced labour resulting in vaginal delivery within 24 h. Instead, the data demonstrate that blockade of progesterone activity by the progesterone antagonist was not sufficient by itself to achieve parturition in these primates. Uterine myometrial contractile activity under RU 486 exposure was not sufficient to induce labour and delivery. Moreover, the progesterone antagonist concentration in breast milk was very low, indicating little passage to suckling newborn infants.
authors.affiliation: Laboratoire de Biologie de la Reproduction, Histologie, Embryologie, Cytogénétique, Centre Hospitalier de Bicêtre, Paris, France.
authors.forename: J P
authors.initials: JP
authors.lastname: Wolf
authors.forename: J
authors.initials: J
authors.lastname: Simon
authors.forename: J
authors.initials: J
authors.lastname: Itskovitz
authors.forename: M J
authors.initials: MJ
authors.lastname: Sinosich
authors.forename: A
authors.initials: A
authors.lastname: Ulmann
authors.forename: E E
authors.initials: EE
authors.lastname: Baulieu
authors.forename: G D
authors.initials: GD
authors.lastname: Hodgen
mesh_terms: D000818:Animals; D002584:Cervix Uteri / Q000187:drug effects / Q000502:physiology; D005260:Female; D007751:Labor, Induced; D007743:Labor, Obstetric / Q000187:drug effects*; D008252:Macaca fascicularis; D015735:Mifepristone / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D008892:Milk / Q000378:metabolism; D011247:Pregnancy; D014590:Uterine Contraction / Q000187:drug effects
chemical_list: D015735:Mifepristone