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Experiments were conducted to investigate the mechanisms through which chronic treatment with estradiol-17beta (E2) prolongs the estrous cycle in the ewe. To determine whether treatment with estradiol maintained the corpus luteum (CL), mature ewes were assigned randomly to two groups receiving s.c. injections of either 500 microg E2 in corn oil or vehicle alone for 20 days beginning on Day 4 of the cycle (n = 5 per group). Laparotomy of E2-treated ewes on Day 24 revealed the presence of CL previously marked with India ink on Day 7 of the cycle. Treatment increased the mean interestrous interval for 4 of 5 animals compared with that of controls (p &lt; 0.001). Therefore, to determine whether the increase in the interestrous interval was due to an effect on the function and/or concentration of uterine oxytocin receptors (OTr), ewes (n = 5 per group) were injected with 500 microg E2 or vehicle as described above from Days 4 to 14 of the cycle. On Day 15, a jugular blood sample was collected for progesterone (P4) analysis, after which ewes were given an i.v. injection of oxytocin (OT; 20 IU USP) or saline, and blood samples were collected at frequent intervals for 60 min to determine plasma concentrations of 13,14-dihydro-15-ketoprostaglandin F2alpha (PGFM). Laparotomies were performed after blood collection to remove uterine endometrium for OTr analysis. Mean serum concentrations of P4 were greater in treated than in control ewes on Day 15 (p &lt; 0.05). Treatment of ewes with E2 prolonged luteal function and resulted in reduced uterine concentration of OTr compared with that of controls (p = 0.002). Treatment with E2 reduced OT-induced plasma concentrations of PGFM compared with controls (p &lt; 0.01). Collectively, these data suggest that chronic treatment of ewes with estradiol during the cycle can prolong the interestrous interval by reducing uterine concentration of OTr and hence OT-induced secretion of prostaglandin.

Down-Regulation of Oxytocin Receptors and Secretion of Prostaglandin F2α after Chronic Treatment of Ewes with Estradiol-17β1