Effects on maternal and fetal steroid concentrations of induction of parturition in the sheep by inhibition of 3 beta-hydroxysteroid dehydrogenase.
Changes in circulating steroid hormones, the incidence of myometrial contractions, and the onset of labour were all monitored after administration of the 3 beta-hydroxysteroid dehydrogenase inhibitor, epostane, to chronically catheterized ewes and fetuses near term. In all animals the drug induced delivery 33-36 h after injection or infusion into the ewe with the birth of live healthy lambs which showed normal subsequent development. Epostane induced immediate, permanent falls in both maternal and fetal plasma progesterone concentrations, accompanied by increased PGF metabolite concentrations in the uterine vein beginning 15 min after treatment. Of the other hormonal changes observed, the most striking was the pronounced drop in both maternal and fetal plasma cortisol. In the fetus this fall was followed by increasing concentrations of circulating ACTH which eventually restored the cortisol levels. By 12-24 h after epostane a substantial overshoot had occurred and at 27-30 h the fetal plasma cortisol concentrations were as high as those seen during normal parturition at term. No significant changes in maternal plasma oestradiol-17 beta could be detected after epostane treatment or during labour. The incidence of slow myometrial contractions increased significantly during the second 3-h period after epostane, although their duration did not change. Contraction patterns typical of first stage labour were seen from 20 to 24 h. These results show that epostane may be used as a safe, predictable inducing agent in sheep if given 6-10 days before term; the lambs showed no signs of prematurity despite their lowered plasma cortisol concentrations which persisted for some hours before labour was induced.
Silver
M
M
Physiological Laboratory, Cambridge, U.K.
D015096:3-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors*; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000737:Androstenols / Q000494:pharmacology*; D000818:Animals; D005260:Female; D005312:Fetal Blood / Q000032:analysis; D006854:Hydrocortisone / Q000097:blood; D007743:Labor, Obstetric / Q000187:drug effects*; D011247:Pregnancy; D011374:Progesterone / Q000097:blood; D011460:Prostaglandins F / Q000378:metabolism; D012756:Sheep / Q000502:physiology*; D014590:Uterine Contraction / Q000187:drug effects
D000737:Androstenols; D011460:Prostaglandins F; D011374:Progesterone; C046855:epostane; D000324:Adrenocorticotropic Hormone; D015096:3-Hydroxysteroid Dehydrogenases; D006854:Hydrocortisone