Release of prostaglandins and leukotrienes from the rat uterus in an early estrogenic response

Abstract

The early estrogenic responses are considered to be involved in inducing embryo implantation in a progesterone (P 4)-primed uterus. Because of their involvement in the process of implantation and decidualization, prostaglandins (PGs) and leukotrienes (LTs) could be the mediators of early estrogenic responses in a P 4-primed uterus. Therefore, temporal effects of estrogen on the production and/or release of PGF 2, PGF 2α, LTB 4 and LTC 4 by the P 4-primed uterus of hypophysectomized rats were examined. Hypophysectomized mature female rats were injected for 4 days with P 4 (2 mg/rat, s.c.) or with P 4 plus a single injection of estradiol-17β (E 2) (100 ng or 200 ng/rat, i.v.) on the last day of P 4 treatment. In one set of experiments, animals were killed at 0.5, 2, 4, 8, 12 and 30h after the last steroid treatment. The production of PGs and LTs by uterine homogenates was measured by radioimmunoassays (RIAs). The production of PGE 2 and PGF 2α in P 4-treated animals showed peaks at 2, 6 and 12 h. The superimposition of E 2 on P 4 treatment induced a higher production rate of PGE 2 and PGF 2α at 0.5h and abolished the peaks induced by P 4 at 2h, but not the peaks at 6 or 12h. Irrespective of the kind of steroid hormonal treatments, uterine production of LTs showed a rapid decline between 6 and 8h followed by a sharp rise at 12h. The superimposition of E 2 on P 4-treatment again increased the production rates of LTB 4 and LTC 4 at early hours, i.e. at 0.5 and 2h, respectively, as compared to P 4 treatment only. In another set of experiments, the in vitro release of PGE 2, PGF 2α, LTB 4 and LTC 4 by uterine explants from hypophysectomized rats receiving P 4 or P 4 + E 2 was measured by RIAs. The spent culture media were collected every hour for 4h. The hourly and cumulative release of PGs by the explants were higher after 1h of P4 + E 2 treatment than after P 4 treatment alone. The release of PGE 2 and PGF 2α increased with time after P 4 treatment, while superimposition of E 2 decreased their release with time. Irrespective of the time of sampling or steroid treatment, the release of PGs during the 1st h was always higher than at other times of culture. The release of PGs from uteri exposed only to P 4 declined between the 1st and 2nd h of incubation but thereafter remained constant. In contrast, the release of PGs declined throughout the incubation period when E 2 was superimposed on P 4 treatment. Much less LTB 4 and LTC 4 were released than PGs, and both LTs were undetectable in the culture media after the 1st h of incubation. The super-imposition of E 2 on P 4 treatment showed a tendency toward a higher release of LTs at 1h as compared to P 4 treatment only.