Uterine Decidual ization in Hypophysectom ized-Ovariectom ized Rats: Effects of Pituitary Hormones1

Decidualization of the endometrial stroma occurs in rats in response to implanting blastocysts or after the application of an appropriately timed artificial stimulus. It is well established that decidualization is regulated by estrogens and progesterone (P). The present study investigated the role of pituitary hormones in this response. Decidualization produced by the bilateral intrauterine injection of 100 μl sesame oil was compared in ovariectomized (OVX) and hypophysectomized (HYPOX)-OVX rats. All animals were treated with a sequence of 17 β-estradiol (E2) and P that in OVX rats supported decidualization. As assessed by uterine weights 5 days after uterine stimulation, decidualization was much greater in OVX than in HYPOX-OVX rats (geometric mean uterine weights of 1539 and 376 mg, respectively). To determine the ability of pituitary hormones to restore decidualization in HYPOX-OVX rats, animals were treated with ovine prolactin (oPRL, 2 x 100 μg daily), bovine growth hormone (bGH, 2 x 125 μg daily), and thyroxine (1 μg/day, replacement for thyrotropin) in addition to E2 and P. Combined treatment with bGH + thyroxine resulted in decidualization which was not significantly different from that obtained in OVX rats; the effects of bGH and thyroxine were additive. oPRL had no significant effect. Administration of bGH + thyroxine during the prestimulation period resulted in decidualization which did not differ significantly from that obtained when the hormones were administered both pre- and poststimulation; administration during the poststimulation period only, when growth and differentiation of decidual cells occurs, resulted in much less decidualization. Because an increase in endometrial vascular permeability is a prerequiste for decidualization, [125I]-labeled bovine serum albumin was used to assess permeability 8 h after uterine stimulation. Uterine concentrations of radioactivity indicated that endometrial vascular permeability was increased to the same extent in bGH + thyroxine-treated HYPOX-OVX rats as in OVX animals; this increase was significantly reduced in vehicle-treated HYPOX-OVX rats. Because prostaglandins (PGs) are involved in decidualization, the possibility that the reduced responses in vehicle-treated HYPOX-OVX rats were a consequence of a decreased capacity of the uterus to produce PGs in response to the deciduogenic stimulus was investigated. As indicated by uterine PGE and PGF concentrations 15 min after uterine stimulation, uterine PGE and PGF production was increased by the stimulus in both vehicle-treated and bGH + thyroxine-treated HYPOX-OVX rats. The ability of PGE2 to induce decidualization when infused unilaterally into the uterine lumen of rats treated with indomethacin to inhibit endogenous PG production was examined. Decidualization was much greater in bGH + thyroxine-treated rats than in controls (geometric mean weights of infused horns of 1102 and 302 mg, respectively). Endometrial membrane preparations from HYPOX-OVX rats treated without or with bGH + thyroxine and from OVX rats were incubated with varying concentrations of [3HJPGE2 without or with an excess of PGE2. Estimates of the apparent dissociation constants and of numbers of binding sites for [3H]PGE2 did not differ signıfıcantly between preparations. These data indicate that in HYPOX-OVX rats, GH and thyroxine are required along with E2 and P to sensitize the uterus for the decidual cell reaction. The effect of GH and thyroxine appears to be independent of uterine PG production and of endometrial binding sites for PGE2.