MECHANISM OF ACTION OF GLUCOCORTICOIDS IN INDUCTION OF OVINE PARTURITION: EFFECT ON PLACENTAL STEROID METABOLISM

Abstract

SUMMARY Maternal plasma progesterone levels in sheep may fall dramatically during the last few days of gestation and following the administration of glucocorticoids to the foetus. To investigate the mechanism of the fall, metabolism of [3H]pregnenolone and/or [3H]progesterone in vitro by ovine placental tissue was studied in five ewes before and after intra-foetal administration of dexamethasone in a dosage sufficient to induce parturition, and in one ewe after the spontaneous onset of labour at 143 days of gestation. Manual separation of maternal and foetal placental tissues showed that, in 11 out of 12 cases, the foetal and not the maternal placenta produced progesterone from pregnenolone in vitro. Total activities of cholesterol side-chain cleavage enzyme and 3β-hydroxysteroid dehydrogenase in the foetal placenta were not influenced by intra-foetal dexamethasone. Before administration of dexamethasone, homogenates of foetal placenta converted [3H]progesterone to 20α-hydroxy [3H]pregn-4-en3-one in the presence of NADPH. Within 12 h of administration of dexamethasone, and after the natural onset of labour at 143 days, large amounts of 17α,20α-dihydroxy[3H]pregn4-en-3-one were formed from [3H]progesterone. Intra-foetal dexamethasone treatment also induced the formation of 17α,20α-dihydroxy[3H]pregn-4-en-3-one by minced foetal placental tissue incubated with [3H]pregnenolone. This change in steroid metabolism did not occur in foetal placental tissue from a sham-operated animal receiving no dexamethasone. Assay of progesterone in foetal placentae showed that the increased formation of 17α,20αdihydroxypregn-4-en-3-one was unlikely to be caused by a change in the specific activity of added 3H-labelled precursor, although the production of 17α,20α-dihydroxypregn-4-en3-one in vitro increased at a time when both foetal placental and utero-ovarian venous levels of progesterone were decreasing in response to dexamethasone treatment. These observations indicate that intra-foetal dexamethasone treatment induces a placental 17α-hydroxylase enzyme, which is also present in foetal placental tissue after the spontaneous onset of labour at term.