Estrogen induced changes in uterine sensitivity for the decidual cell reaction: interactions between prostaglandin E2...

In rats receiving high doses of estrogen along with progesterone, the uterus is desensitized and does not respond to artificial stimuli with increased endometrial vascular permeability or decidualization. In addition, prostaglandin E2 (PGE2), the putative mediator of endometrial vascular permeability changes in sensitized uteri, is ineffective when given into the uterine lumen. The possibility that this inability of PGE2 to increase endometrial vascular permeability may be related to the unavailability of histamine or bradykinin was investigated. Rats were differentially sensitized for the decidual cell reaction by the daily injection of 2 mg progesterone with either 0.5 or 10 microgram estrone for the 3 days preceding the unilateral intra-uterine injection of 50 microliters phosphate buffered saline containing gelatin with or without 10 microgram PGE2 and with or without 1 mg histamine or 1 microgram bradykinin. Prior to the intrauterine injection, all rats were treated with indomethacin to inhibit endogenous prostaglandin production. Endometrial vascular permeability changes were determined 8 h later by determining radioactivity levels in injected and non-injected uterine horns 15 min after the i.v. injection of 125I-labelled bovine serum albumin. PGE2 increased endometrial vascular permeability in rats receiving 0.5 microgram estrone, but not in those receiving 10 microgram. Histamine or bradykinin, alone or with PGE2, did not affect endometrial vascular permeability in rats receiving either estrogen dose. The data suggest that the unresponsiveness of uteri from rats treated with high doses of estrogen is not simply due to the unavailability of bradykinin or histamine.