Trilostane but not prostaglandin F2alpha (PGF2alpha) or cortisol aborts 90-day-pregnant lutectomized sheep

Ewes were lutectomized and treatments were started 72 h later. Pregnant ewes were treated with vehicle; prostaglandin F2alpha (PGF2alpha); cortisol (C); trilostane (TR), a 3beta-hydroxy-steroid dehydrogenase inhibitor; PGF2alpha + C; TR + PGF2alpha; TR + C, or TR + PGF2 + C. TR, TR + PGF2alpha, TR + C, and TR + PGF2alpha + C aborted (P < or = 0.05) all ewes receiving TR. One ewe treated with PGF2alpha aborted (P > or = 0.05). The average time to abortion of TR-treated ewes was 50.8 h (P < or = 0.05) after initiation of treatments. All aborted ewes had retained placentas (P < or = 0.05) except one ewe in the TR + PGF2alpha, treatment group. TR was given every 12 h starting at 72 h postlutectomy until 96 h postlutectomy. TR reduced (P < or = 0.05) progesterone. Estradiol-17beta was increased (P < or = 0.05) 2 h after the first two TR treatments and declined 2 h later and was followed by a sustained increase (P < or = 0.05) in estradiol-17beta, which was coincident with the onset of abortions. Estradiol-17beta was increased (P < or = 0.05) by PGF2alpha but did not decrease (P > or = 0.05) placental secretion of progesterone. It is concluded that TR but not PGF2alpha is an abortifacient in 90-day-pregnant lutectomized ewes and that abortion occurs only when there is a decrease in circulating progesterone and an increase in circulating estradiol-17beta.