Prostaglandin synthesis from endogenous and exogenous arachidonic acid in the rat uterus. Effect of estradiol and progesterone

Abstract

Regulation of uterine prostaglandin (PG) synthesis by steroid sex hormones was studied in female rats. Animals were ovariectomized (OVX) and received silastic implants of estradiol (E2) or progesterone (Pg); the implants were maintained for 7 days. The animals were sacrificed and their uteri homogenized at 4°C. Basal levels of PGs and PGs synthesized during 20 min incubations at 37°C , either without exogenous arachidonic acid (AA), or in the presence of 2.10 −5 M added AA were measured by RIA. Comparison between the various treatments shows that the regulation of uterine PG synthesis in the rat is a multistep process and depends on the type of PG. PGI 2 (6 keto PGF 1α) is synthesised in very large amounts but is not very significantly influenced by hormonal treatment. PGF 2α and PGE 2 are synthesized in much smaller quantities but are very dependent on hormonal treatment. E 2 stimulates PGF 2α and inhibits PGE 2, shifting the ratio from 0.5 in untreated OVX rats to 3.3 in OVX E2-treated rats. TXA 2 (TXB 2) is stimulated by E2. Pg significantly stimulates endogenous PGF 2α levels but does not changethe profile of PGs synthesized from the endogenous substrate. It inhibits PGE 2 synthesis from exogenously added AA. These results show that E2 favors PGF 2α synthesis at the expense of PGE 2 and that the synthesis of PGI 2, which is the main AA metabolite in the rat uterus is not hormone dependent, (at least not under the conditions of our experiments).