Impact of chronic treatment of ewes with estradiol-17β or progesterone on oxytocin receptor gene transcription and ovarian oxytocin secretion

Three experiments were conducted, the objectives of which were to 1) examine the effects of exogenous estradiol (E-2) and progesterone (P-4) on uterine concentrations of oxytocin receptors (OTR) and OTR mRNA, as well as the effect of exogenous P-4 on progesterone receptors (PR) during the late luteal phase of the cycle, and 2) ascertain whether chronic E-2 treatment of ewes during the cycle would alter prostaglandin F-2 alpha (PGF(2 alpha))-induced secretion of luteal oxytocin (OT). In experiment 1, 15 ewes were assigned to a control (n = 5; 2 ml corn oil [CO] s,c, on Days 4-14 of the estrous cycle) and two treatment groups in = 5 each) receiving either 250 mu 8 E-2 s,c. (Days 4-14) or 10 mg P-4 s.c. (CO on Days 4-10 and P-4 on Days 11-14). Endometria and corpora lutea were removed on Day 15 of the cycle, Mean luteal weights were greater in treated than in control ewes (p < 0.05). Endometrial concentrations of OTR and OTR mRNA were significantly greater in control than in E-2- or P-4-treated ewes, In experiment 2, five ewes each were treated s.c. with CO or 10 mg P-4 on Days 11-14 of the cycle; endometria were then removed on Day 15 for PR assay. Endometrial concentration of PR did not differ between groups. Experiment 3 consisted of 20 ewes assigned to four groups in a 2 x 2 factorial arrangement. Treatment consisted of two dosages of E-2 (0 or 250 mu g/day) in 2 mi CO and two dosages of PGF(2 alpha) analogue (0 or 125 mu g Estrumate). All ewes were injected s.c. with E-2 or CO for 11 days as described for experiment 1. On Day 15, all ewes received an i.v. injection of PCF2 alpha or saline (Time 0); then jugular blood was collected at frequent intervals for analysis of serum concentrations of OT. PCF2 alpha induced a release of OT in control and E(2-)treated ewes (p < 0.05) compared to the value in saline-treated ewes. Collectively, these data suggest that in cycling ewes, exposure of the uterus to increased concentrations of E-2- or P-4 causes down-regulation of OTR as a consequence of suppression of the OTR gene. Chronic E-2 treatment of ewes during the cycle does not act directly on the ovary to alter the stores of luteal OT.