INHIBITION AND AUGMENTATION OF PROGESTERONE PRODUCTION DURING PREGNANCY - EFFECTS ON PARTURITION IN RHESUS-MONKEYS

OBJECTIVES: Uterine quiescence during mammalian pregnancy is attribute d to progesterone. However. systemic progesterone levels remain elevat ed in primates before parturition. Epostane, a selective 3 beta-hydrox ysteroid dehydrogenase inhibitor, and progesterone (with or without ep ostane) were administered to late pregnant rhesus monkeys to clarify t he role of progesterone in primate parturition. STUDY DESIGN: On days 122 to 132 of gestation (term 167 days), 11 rhesus monkeys (Macaca mul atta) with timed pregnancies were divided into three treatment groups: (1) epostane alone (10 mg/kg subcutaneously), (2) epostane with proge sterone subcutaneously in Silastic silicone rubber capsules, and (3) p rogesterone implants only with no surgical instrumentation. Maternal a nd fetal blood and amniotic fluid were sampled for progesterone, estro ne, estradiol, cortisol, testosterone, androstenedione, dehydroepiandr osterone, dehydroepiandrosterone sulfate, and amniotic fluid was sampl ed for prostaglandins E(2) and F-2 alpha. Uterine activity was monitor ed continuously by electromyography and intraamniotic pressure. Cervic al status was assessed by a modified Bishop's score. Production of pro staglandins E(2) and F-2 alpha by amnion was determined by tissue supe rfusion. The group of three noninstrumented monkeys, which received on ly progesterone Silastic silicone rubber implants subcutaneously at 14 6 to 148 days, were observed until spontaneous vaginal delivery. RESUL TS: Epostane reduced maternal and fetal progesterone levels by 75% and 50%, respectively, followed by increased uterine activity and cervica l ripening within 24 hours and vaginal delivery within 48 hours. Amnio tic fluid progesterone decreased to undetectable levels. Progesterone implants prevented the epostane-induced decrease in maternal and fetal progesterone levels and the associated myometrial and cervical change s until the implants were removed. Alterations in other steroid hormon es were consistent with inhibition of 3 beta-hydroxysteroid dehydrogen ase. Amniotic prostaglandin E(2) production was increased sixfold by e postane (p < 0.05) but did not reach the high levels normally seen at spontaneous parturition. Animals that received progesterone implants a lone had markedly elevated circulating progesterone concentrations yet were delivered spontaneously at term (range 163 to 167 days). CONCLUS IONS: Progesterone withdrawal induces preterm labor and delivery (whic h can be blocked by progesterone substitution) but exogenous progester one, even in substantial quantities, does not prevent parturition at t erm.