Increase in concentration of uterine oxytocin receptors and decrease in response to 13,14-dihydro-15-keto prostaglandin F2α in ewes after withdrawal of exogenous progesterone
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Summary. Ovariectomized ewes were treated with progesterone and oestradiol to induce oestrus (day of expected oestrus = day 0) and with progesterone on days 1 to 12. The concentrations of endometrial oxytocin receptors and the 13,14-dihydro-15-keto prostaglandin F2α (PGFM) response induced by oxytocin were measured on days 12, 14, 16 and 18 after the cessation of progesterone treatment on day 12, by a receptor binding assay and direct radioimmunoassay, respectively. During the period of treatment, the concentrations of plasma progesterone were high and remained above 2 ng ml−1 until day 13 when they dropped rapidly to less than 0·5 ng ml−1 by day 14. The concentrations of oxytocin receptors in endometrium of control ewes were high (820·7 ± 91·7 (sem) fmol mg−1 protein). Treatment with progesterone significantly (P < 0·01) reduced the concentrations of the receptors on days 12 and 14 (144·1 ± 65·0 and 200·4 ± 45·4 fmol mg−1 protein, respectively). The receptor concentrations then increased to relatively high values on day 16 (1021·4 ± 216·6 fmol mg−1 protein) and remained high until day 18 (677·7 ± 103·4 fmol mg−1 protein). In contrast, the oxytocin-induced PGFM response was low in control ewes (2·7 ± 1·5 ng min−1 ml−1 and 74·2 ± 29·9 pg ml−1, for the area under the curve and peak concentrations, respectively), and treatment with progesterone did not increase the response on day 12 (2·2 ± 0·8 ng min−1 ml−1 and 99·3 ± 42·9 pg ml−1; but, on day 14 the response (13·3 ± 2·9 ng min−1 ml−1 and 297·1 ± 55·2 pg ml−1) was significantly (P < 0·02) higher than those observed in the control ewes or day 12 ewes. The oxytocin-induced response declined rapidly after day 14, and by day 16 and 18, the PGFM response induced by oxytocin (7·9 ± 2·7 ng min−1 ml−1 and 188·3 ± 48·0 pg ml−1; 1·6 ± 0·3 ng min−1 ml−1 and 58·9 ± 11·8 pg ml−1, for days 16 and 18, respectively) was not significantly (P > 0·05) different from those in the control ewes or day 12 ewes. These results confirm previous reports suggesting that treatment with progesterone can suppress the concentrations of endometrial oxytocin receptors while simultaneously increasing the PGFM response induced by oxytocin. The results also show that the withdrawal of exogenous progesterone alone is followed by a rapid increase in the endometrial concentration of oxytocin receptors and a reduction in the PGFM response induced by oxytocin.
Keywords: progesterone; oxytocin; receptor; uterus; sheep
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