QUANTITATIVE CONTROL OF OXYTOCIN-INDUCED PGF(2-ALPHA) RELEASE BY PROGESTERONE AND ESTRADIOL IN EWES

The effect of oestradiol and progesterone concentrations on the uterin e PGF(2 alpha) response to oxytocin was investigated by measuring 13,1 4-dihydro-15-keto PGF(2 alpha) (PGFM) secretion. One week after ovarie ctomy, 27 ewes were administered progestagen for 10 days followed by o estradiol for 2 days. Day 0 was designated as the time of the last 'oe strous' oestradiol injection. Six groups of ewes (n = 4) were then tre ated for 12 days with a high or low dose of progesterone (36 or 12 mg day(-1)) either alone or with a high or low dose of oestradiol (36 or 12 mu g day(-1)) administered (in 1 ml of corn oil by i.m. injection, at intervals of 8 h) in a pattern designed to simulate a natural oestr ous cycle profile. A control group (n = 3) was given corn oil alone. E wes were treated with 1 mu g oxytocin (i.v.) on days 4, 8 and 12 of th e simulated cycle and plasma was collected for assay of PGFM. An oxyto cin-induced PGFM response occurred only on day 12, when the response w as suppressed by high doses of progesterone and stimulated by high oes tradiol doses. There was a significant effect of progesterone (P < 0.0 5) and a highly significant effect of oestradiol (P < 0.01) on the pat tern of PGFM release in response to oxytocin. Low progesterone/high oe stradiol stimulated the largest and most sustained increase in PGFM fo llowing oxytocin. There was a significant relationship between the oes tradiol:progesterone ratio and the mean PGFM response on day 12 (P < 0 .05). This is the first demonstration of a quantitative effect of ster oid hormone concentrations on the PGFM response to oxytocin in ewes, a nd indicates that in early pregnancy, ewes with a high oestradiol:prog esterone ratio may generate larger PGF(2 alpha) episodes thus increasi ng the risk of a failure of the maternal recognition of pregnancy.