Failure of luteolysis and extension of the interoestrous interval in sheep treated with the progesterone antagonist mifepristone (RU 486).
The progesterone antagonist mifepristone (RU 486) was injected i.m. into ewes during the early luteal phase of the oestrous cycle to test the hypothesis that duration of uterine exposure to progesterone from the corpus luteum initiates luteolysis through the proper timing of endometrial oxytocin receptor expression and pulsatile secretion of PGF2 alpha coincident with release of luteal oxytocin. In Expt 1, duration of cycle, the PGF2 alpha metabolite 15-keto-13,14-dihydro-PGF2 alpha (PGFM) and oxytocin concentrations were measured in ewes treated on days 5, 6, 7 and 8 of the oestrous cycle with either 2.5 or 5.0 mg RU 486 kg-1 day-1 (n = 4 per group); control ewes (n = 6) were injected i.m. with 80% ethanol (diluent). In Expt 2, the presence of functional uterine oxytocin receptors was determined indirectly on day 12 of the cycle by measuring the plasma PGFM response to oxytocin challenge (20 iu, i.v.) in diluent-treated ewes (n = 3) and in ewes treated with 2.5 mg RU 486 kg-1 day-1 on days 6, 7 and 8 of the oestrous cycle. Duration of the oestrous cycle of control ewes (16 +/- 1 days) was extended beyond day 24 (day 0 = oestrus) in 10 of 11 ewes treated with RU 486 as determined by daily exposure of ewes to a ram and by measurement of progesterone concentrations in plasma in the two experiments.(ABSTRACT TRUNCATED AT 250 WORDS)
Morgan
G L
GL
Department of Veterinary Medicine, Oklahoma State University, Stillwater 74078.
Geisert
R D
RD
McCann
J P
JP
Bazer
F W
FW
Ott
T L
TL
Mirando
M A
MA
Stewart
M
M
D000818:Animals; D015237:Dinoprost / Q000031:analogs & derivatives / Q000097:blood; D004717:Endometrium / Q000378:metabolism; D004971:Estrus / Q000187:drug effects; D005260:Female; D003341:Luteolysis / Q000187:drug effects*; D015735:Mifepristone / Q000494:pharmacology*; D010121:Oxytocin / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D011374:Progesterone / Q000097:blood; D018045:Receptors, Oxytocin / Q000378:metabolism; D012756:Sheep / Q000097:blood / Q000502:physiology*
D018045:Receptors, Oxytocin; C008228:15-keto-13,14-dihydroprostaglandin F2alpha; D015735:Mifepristone; D011374:Progesterone; D010121:Oxytocin; D015237:Dinoprost