Effects of Progesterone and Estradiol-17β on Uterine Secretion of Prostaglandin F2α in Response to Oxytocin in Ovariectomized Ewes1

Abstract

Twenty ovariectomized ewes were used in an experiment designed to examine the interaction of progesterone, estradiol, and oxytocin in the regulation of uterine secretion of prostaglandin F2.alpha. (PGF2.alpha.). All ewes underwent a steroid pretreatment that mimicked the changes in progesterone and estradiol which occur during the six days immediately prior to estrus. After pretreatment, ewes were randomly assigned to 1 of 4 treatment groups: 1) control (n = 4); 2) estradiol-17.beta. (n = 6); 3) progesterone (n = 4); and 4) progesterone and estradiol-17.beta. (n = 6). Progesterone was injected twice daily for 15 days. The dose of progesterone varied with day postestrus in a manner designed to simulate endogenous luteal secretion of progesterone. Estradiol-17.beta. was administered in s.c. Silastic implants. The implants maintained circulating concentrations of estradiol at 3 pg/ml. On Days 5, 10, and 15 of treatment, ewes were injected with oxytocin (10 IU in 1.0 ml saline, i.v.). Jugular venous blood samples were collected beginning one-half hour prior to and continuing for 2 hours post-oxytocin injection for quantification of 13,14-dihydro-15-keto-prostaglandin F2.alpha. (PGFM). No changes in concentration of PGFM following injection of oxytocin were observed on Day 5 or 10 in any treatment group. Concentration of PGFM increased following injection of oxytocin on Day 15 only in groups receiving progesterone. Both the area under the PGFM response curve (p = 0.08) and peak response (p = 0.06) were greater in ewes treated with progesterone and estradiol-17.beta. than in those receiving progesterone alone. It was concluded that 15 days of treatment with progesterone can restore uterine responsiveness to oxytocin in ovariectomized ewes and that estradiol can enhance the effect of progesterone.