Effect of mifepristone on pregnancy, pregnancy-specific protein B (PSPB), progesterone, estradiol-17beta, prostaglandin F2alpha (PGF2alpha) and prostaglandin E (PGE) in ovariectomized 90-day pregnant ewes.
The objective of this experiment was to determine the effect of mifepristone, a progesterone receptor antagonist, on pregnancy and secretion of steroids, pregnancy-specific protein B (PSPB) and prostaglandins at mid-pregnancy in ewes. Ninety-day pregnant ewes were ovariectomized (OVX) and treatments were initiated 72 h post-OVX. Ewes received (1) vehicle, (2) prostaglandin F2alpha (PGF2alpha, 8 mg/58 kg/bw, i.m.) 84 h post-OVX, (3) mifepristone (50 mg intrajugular at 72, 84, 96, and 108 h post-OVX), (4) mifepristone (50mg) + PGF2alpha, (5) mifepristone (100 mg intrajugular at 72, 84, 96, and 108 h), and (6) mifepristone (100 mg) + PGF2alpha. Ewes treated with vehicle or PGF2alpha alone did not abort (P > or = 0.05). But, 60, 80, 60, and 100% of ewes treated with mifepristone (50 mg), mifepristone (50 mg) + PGF2alpha, mifepristone (100 mg), and mifepristone (100 mg) + PGF2alpha, respectively, aborted (P < or = 0.05). Profiles of progesterone, estradiol-17beta, prostaglandin E (PGE), or PSPB did not differ (P > or = 0.05) among treatment groups. Profiles of PGF2alpha of treatment groups receiving mifepristone with or without PGF2alpha differed (P < 0.05) from vehicle or PGF2alpha alone-treated ewes. It is concluded that progesterone actions are necessary to suppress uterine/placental secretion of PGF2alpha and that maintenance of critical progesterone: estradiol-17beta and PGE:PGF2alpha ratios are necessary for maintenance of pregnancy.
Weems
Y S
YS
Department of Human Nutrition, Food and Animal Sciences, University of Hawaii, Honolulu 96822, USA.
Bridges
P J
PJ
Sasser
R G
RG
Ching
L
L
LeaMaster
B R
BR
Vincent
D L
DL
Weems
C W
CW
D000028:Abortion, Induced / Q000662:veterinary; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000187:drug effects; D015237:Dinoprost / Q000378:metabolism*; D004958:Estradiol / Q000378:metabolism; D005260:Female; D015735:Mifepristone / Q000494:pharmacology*; D010052:Ovariectomy; D010053:Ovary / Q000502:physiology*; D011247:Pregnancy; D011255:Pregnancy Maintenance; D011257:Pregnancy Proteins / Q000187:drug effects; D011270:Pregnancy, Animal / Q000187:drug effects*; D011458:Prostaglandins E / Q000378:metabolism; D011980:Receptors, Progesterone / Q000037:antagonists & inhibitors*; D012756:Sheep
D011257:Pregnancy Proteins; D011458:Prostaglandins E; D011980:Receptors, Progesterone; D015735:Mifepristone; D004958:Estradiol; D015237:Dinoprost; D016282:Aspartic Acid Endopeptidases; C094766:pregnancy-associated glycoprotein 1