Effects of progesterone and estradiol on prostaglandin endoperoxide synthase in ovine endometrial tissue

Abstract

In experiment 1, 20 ovariectomized ewes were used to determine how progesterone and estradiol interact to regulate endometrial concentration and activity of prostaglandin endoperoxide synthase (PGS). Ewes were randomly assigned to one of four treatment groups: (1) control ( n = 5); (2) estradiol ( n = 5); (3) progesterone ( n = 5); (4) progesterone and estradiol ( n = 5). Groups 3 and 4 received twice daily injections of progesterone for 15 days. The dose of progesterone was varied to simulate concentrations of progesterone observed in intact ewes during the estrous cycle. Estradiol was administered to groups 2 and 4 by subcutaneous silastic implants which maintained circulating concentrations of estradiol of approximately 3 pg ml −1. Ewes were slaughtered on day 16. A portion of uterine tissue was fixed and stained, immunohistochemically, for PGS. Treatment with progesterone induced an increase in epithelial cell height ( P < 0.01) and an increase in intensity of staining for PGS in epithelial cells ( P < 0.01). Explants of caruncular endometrial tissue were collected from each ewe and incubated in the presence or absence of arachidonic acid (20 μg ml −1) to quantify release of PGF 2α, in vitro. Release of PGF 2α in the presence of arachidonic acid was used as a functional assessment of PGS activity. Release was greater for tissue collected from groups treated with progesterone ( P < 0.01). Within progesterone treated groups, release was greater for tissue from ewes that also received estradiol ( P < 0.05). Release of PGF 2α was enhanced by the addition of arachidonic acid ( P < 0.01). Maximal release of PGF 2α in the presence of arachidonic acid was observed in tissue from ewes receiving progesterone and estradiol. In experiment 2, 19 ewes were randomly assigned to one of four treatment groups: (1) control ( n = 4); (2) estradiol ( n = 5); (3) progesterone ( n = 5); (4) progesterone and estradiol ( n = 5). Steroids were administered as in experiment 1 with minor modification in doses of progesterone. Uteri were collected on day 16. Explants of caruncular endometrial tissue were incubated in the presence of one of four treatments: (1) no additions; (2) arachidonic acid (20 μg ml −1); (3) oxytocin (10 −6 M); (4) arachidonic acid and oxytocin. The effects of ovarian steroids on release of PGF 2α from caruncular endometrial explants were similar to those described in experiment 1. Both arachidonic acid and oxytocin increased release of PGF 2α ( P < 0.01, P < 0.01, respectively). However, release of PGF 2α was not enhanced by arachidonic acid when administered in the presence of oxytocin. We conclude that the ability of ovarian steroids to regulate endometrial secretion of PGF 2α may be exerted, in part, through their ability to regulate the concentration and activity of PGS.