ESTRADIOL CONCENTRATION AND THE DEVELOPMENT OF THE UTERINE OXYTOCIN RECEPTOR AND OXYTOCIN-INDUCED PGF(2-ALPHA) RELEASE IN EWES

The control of temporal changes in oxytocin receptor concentrations an d oxytocin-induced 13,14-dihydro-15-keto PGF(2 alpha) (PGFM) release w as examined in ewes. One week after ovariectomy, 36 ewes were administ ered fluorogesterone acetate for 10 days followed by oestradiol (3 x 1 6 mu g day(-1)) for 2 days (pretreatment cycle). Day 0 was designated as the time of the final 'oestrous' oestradiol injection. Ewes were th en treated for up to 12 days with progesterone (24 mg day(-1) maximum) with or without oestradiol (both hormones administered in 1 ml of cor n oil i.m. at 8 h intervals) in a pattern known to simulate natural pl asma profiles of the oestrous cycle. The three treatments were zero oe stradiol, low oestradiol (12 mu g day(-1) maximum), and high oestradio l (36 mu g day-1 maximum). Subgroups of four ewes from each treatment group were given 1 mu g of oxytocin (i.v.) on day 10, 11 or 12 of the simulated cycle, and endometrial oxytocin receptor concentrations were determined in samples collected within 3 h of oxytocin administration . On day 10 only one ewe in each group exhibited a PGFM response to ox ytocin, and the mean response was unaffected by the concentration of o estradiol administered. On days 11 and 12 there was a significant effe ct of oestradiol concentration (P < 0.05) on the pattern of PGFM relea se in response to oxytocin, the high oestradiol concentration causing a rapid increase in the concentration of PGFM following oxytocin admin istration. On day 12 the oestradiol concentration was positively corre lated with the PGFM mean response (P < 0.01). Oxytocin receptor concen trations were positively correlated with the concentration of PGFM rel eased on days 11 and 12. We conclude that the quantitative effect of o estradiol is mediated principally through the oestrogenic stimulation of uterine oxytocin receptors, although additional effects on post-rec eptor events cannot be excluded. These results demonstrate that the oe stradiol concentration affects the timing, the magnitude and the patte rn of the PGF(2 alpha) response to oxytocin in progesterone-treated ov ariectomized ewes. In the natural cycle, a high oestradiol concentrati on may therefore be associated with an earlier onset of luteolysis.