DOWN-REGULATION OF OXYTOCIN RECEPTORS AND SECRETION OF PROSTAGLANDIN-F2-ALPHA AFTER CHRONIC TREATMENT OF EWES WITH ESTRADIOL-17-BETA

Experiments were conducted to investigate the mechanisms through which chronic treatment with estradiol-17 beta (E-2) prolongs the estrous c ycle in the ewe. To determine whether treatment with estradiol maintai ned the corpus luteum (CL), mature ewes were assigned randomly to two groups receiving s.c. injections of either 500 mu g E-2 in corn oil or vehicle alone for 20 days beginning on Day 4 of the cycle (n = 5 per group). Laparotomy of E-2-treated ewes on Day 24 revealed the presence of CL previously marked with India ink on Day 7 of the cycle. Treatme nt increased the mean interestrous interval for 4 of 5 animals compare d with that of controls (p < 0.001). Therefore, to determine whether t he increase in the interestrous interval was due to an effect on the f unction and/or concentration of uterine oxytocin receptors (OTr), ewes (n = 5 per group) were injected with 500 mu g E-2 or vehicle as descr ibed above from Days 4 to 14 of the cycle. On Day 15, a jugular blood sample was collected for progesterone (P-4) analysis, after which ewes were given an i.v. injection of oxytocin (OT; 20 IU USE) or saline, a nd blood samples were collected at frequent intervals for 60 min to de termine plasma concentrations of 13,14-dihydro-15-keto-prostaglandin F -2 alpha (PGFM). Laparotomies were performed after blood collection to remove uterine endometrium for OTr analysis. Mean serum concentration s of P-4 were greater in treated than in control ewes on Day 15 (p < 0 .05). Treatment of ewes with E-2 prolonged luteal function and resulte d in reduced uterine concentration of OTr compared with that of contro ls (p 0.002). Treatment with E-2 reduced OT-induced plasma concentrati ons of PGFM compared with controls (p < 0.01). Collectively, these dat a suggest that chronic treatment of ewes with estradiol during the cyc le can prolong the interestrous interval by reducing uterine concentra tion of OTr and hence OT-induced secretion of prostaglandin.