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 and oxytocin-induced 13,14-dihydro-15-keto PGF(2 alpha) (PGFM) release was examined in ewes. One week after ovariectomy, 36 ewes were administered fluorogesterone acetate for 10 days followed by oestradiol (3 x 16 mu g day(-1)) for 2 days (pretreatment cycle). Day 0 was designated as the time of the final 'oestrous' oestradiol injection. Ewes were then treated for up to 12 days with progesterone (24 mg day(-1) maximum) with or without oestradiol (both hormones administered in 1 ml of corn oil i.m. at 8 h intervals) in a pattern known to simulate natural plasma profiles of the oestrous cycle. The three treatments were zero oestradiol, low oestradiol (12 mu g day(-1) maximum), and high oestradiol (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 oxytocin, and the mean response was unaffected by the concentration of oestradiol administered. On days 11 and 12 there was a significant effect of oestradiol concentration (P < 0.05) on the pattern of PGFM release in response to oxytocin, the high oestradiol concentration causing a rapid increase in the concentration of PGFM following oxytocin administration. On day 12 the oestradiol concentration was positively correlated with the PGFM mean response (P < 0.01). Oxytocin receptor concentrations were positively correlated with the concentration of PGFM released on days 11 and 12. We conclude that the quantitative effect of oestradiol is mediated principally through the oestrogenic stimulation of uterine oxytocin receptors, although additional effects on post-receptor events cannot be excluded. These results demonstrate that the oestradiol concentration affects the timing, the magnitude and the pattern of the PGF(2 alpha) response to oxytocin in progesterone-treated ovariectomized ewes. In the natural cycle, a high oestradiol concentration may therefore be associated with an earlier onset of luteolysis.