Induction of parturition by cortisol: effects on negative feedback sensitivity and plasma CRF.

In fetal sheep, plasma concentrations of both adrenocorticotropic hormone (ACTH) and cortisol increase at the end of gestation. The increase in fetal plasma cortisol concentration induces placental 17 alpha-hydroxylase and 17, 20 lyase activities and therefore stimulates the placenta to secrete relatively more estrogen and relatively less progesterone. The resultant increase in the estrogen-to-progesterone ratio is thought to increase uterine contractility and initiate labour. We had previously demonstrated that the efficacy of cortisol-induced suppression of ACTH secretion at the end of gestation was reduced. We hypothesized that cortisol-induced stimulation of placental steroidogenesis promoted the secretion of a steroid hormone which reduced negative feedback efficacy, and therefore allowed both ACTH and cortisol secretion to increase simultaneously. Others had proposed that cortisol stimulates the placental secretion of corticotrophin releasing factor, which might also stimulate fetal ACTH secretion. This study was designed to test the hypotheses that cortisol reduces its own feedback efficacy or stimulates CRF secretion. Five pregnant ewes with twin pregnancies were studied after chronic catheterization. One fetus was subjected to infusion of hydrocortisone sodium succinate (10 micrograms/min, iv) and the other to infusion of saline. After 5 and 53 h of infusion, each fetus was subjected to a period of hypotension produced by infusion of sodium nitroprusside. The infusion of hydrocortisone sodium succinate decreased plasma progesterone concentrations in the fetal circulation into which the steroid was infused, and in the maternal circulation. Fetal plasma CRF concentrations were increased on the third day of infusion, the day in which the fetuses went into labour.(ABSTRACT TRUNCATED AT 250 WORDS)