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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 degrees C. Basal levels of PGs and PGs synthesized during 20 min incubations at 37 degrees 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. PGI2 (6 keto PGF1 alpha) is synthesised in very large amounts but is not very significantly influenced by hormonal treatment. PGF2 alpha and PGE2 are synthesized in much smaller quantities but are very dependent on hormonal treatment. E2 stimulates PGF2 alpha and inhibits PGE2, shifting the ratio from 0.5 in untreated OVX rats to 3.3 in OVX E2-treated rats. TXA2 (TXB2) is stimulated by E2. Pg significantly stimulates endogenous PGF2 alpha levels but does not change the profile of PGs synthesized from the endogenous substrate. It inhibits PGE2 synthesis from exogenously added AA. These results show that E2 favors PGF2 alpha synthesis at the expense of PGE2 and that the synthesis of PGI2, which is the main AA metabolite in the rat uterus is not hormone dependent, (at least not under the conditions of our experiments).

Cytosols of rat and guinea pig liver and of human placenta were screened for their capacity to catalyze the conversion of racemic leukotriene A4 into 5S, 12R-dihydroxy-(Z,E,E,Z)-6,8,10,14-eicosatetraenoic acid (leukotriene B4). The epoxide hydrolase activities showed some specificity for the 5S,6S-oxido-(E,E,Z,Z)-7,9,11,14-eicosatetraenoic acid (LTA4) and produced mixtures of leukotriene B4 and its enantiomer containing up to 78-87% of leukotriene B4.