Estrogen and uterine sensitization for the decidual cell reaction: role of prostaglandins.

Abstract

The possibility that the synergistic effect of estrogens, in low dosages, on the decidual cell reaction is related to the ability of the uterus to produce prostaglandins or to respond to prostaglandins with increased endometrial vascular permeability was examined in rats. Immature rats, treated with hormones and ovariectomized so that they were at the equivalent of Day 5 of pseudopregnancy, were used. Groups of rats were differentially sensitized for the decidual cell reaction by the daily injection of 2 mg progesterone with either 0, 1, or 10 µg estrone for the 3 days preceding the application of a deciduogenic stimulus, the unilateral intraluminal injection of 50 µl phosphate buffered saline containing gelatin. Uterine decidualization was greatest in rats receiving 1 µg estrone. As indicated by radioactivity levels in the injected, compared with the noninjected horns 15 min after an i.v. injection of 125I-labeled bovine serum albumin ([125I]-BSA), endometrial vascular permeability was increased 8 h after stimulation; the increase did not differ for rats receiving 0 or 1 µg estrone, but was much less in those receiving 10 µg estrone. Indomethacin, an inhibitor of prostaglandin synthesis, inhibited the permeability response to the deciduogenic stimulus. Uterine prostaglandin production was assessed by determining uterine prostaglandin concentrations; levels of prostaglandins E and F were elevated in the stimulated compared with the nonstimulated horns in rats receiving 0 or 1 µg estrone, but not in those receiving the higher dose. To determine uterine responsiveness to prostaglandins, 10 µg prostaglandin E2 or its vehicle was injected into the uterine lumen of rats treated with indomethacin to inhibit endogenous prostaglandin production. Intrauterine prostaglandin E2 increased permeability to a similar extent in rats receiving 0 or 1 µg estrone, but had no effect in those receiving 10 µg estrone. These results further indicate that prostaglandins, probably of the E-series, mediate the changes in endometrial vascular permeability following a deciduogenic stimulus. For animals receiving 0 or 1 µg estrogen, uterine prostaglandin production and uterine responsiveness to prostaglandins do not appear to account for the synergistic effect of estrogen on the decidual cell reaction. However, the absence of a decidual cell reaction in rats receiving a high dose of estrogen may be due to the inability of the uterus to respond to prostaglandins with increased endometrial vascular permeability.