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Quantitative control of oxytocin-induced PGF₂ release by progesterone and oestradiol in ewes

The effect of oestradiol and progesterone concentrations on the uterine PGF₂ response to oxytocin was investigated by measuring 13,14-dihydro-15-keto PGF₂ (PGFM) secretion. One week after ovariectomy, 27 ewes were administered progestagen for 10 days followed by oestradiol for 2 days. Day 0 was designated as the time of the last 'oestrous' oestradiol injection. Six groups of ewes (n = 4) were then treated 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 µg 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 oestrous cycle profile. A control group (n = 3) was given corn oil alone. Ewes were treated with 1 µg oxytocin (i.v.) on days 4, 8 and 12 of the simulated cycle and plasma was collected for assay of PGFM. An oxytocin-induced PGFM response occurred only on day 12, when the response was suppressed by high doses of progesterone and stimulated by high oestradiol doses. There was a significant effect of progesterone (P < 0.05) and a highly significant effect of oestradiol (P < 0.01) on the pattern of PGFM release in response to oxytocin. Low progesterone/high oestradiol stimulated the largest and most sustained increase in PGFM following oxytocin. There was a significant relationship between the oestradiol:progesterone ratio and the mean PGFM response on day 12 (P < 0.05). This is the first demonstration of a quantitative effect of steroid hormone concentrations on the PGFM response to oxytocin in ewes, and indicates that in early pregnancy, ewes with a high oestradiol:progesterone ratio may generate larger PGF₂ episodes thus increasing the risk of a failure of the maternal recognition of pregnancy.

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