Summary. Prostaglandin precursor fatty acids, predominantly arachidonic acid, were found in the different lipid classes of guinea-pig uterus and plasma on Days 7 and 15 of the oestrous cycle. Of the total arachidonic acid in the uterus, 93% was esterified to uterine phospholipids, of which 80% was bound to phosphatidylcholine and phosphatidylethanolamine. There was a significant decrease in the quantity of arachidonic acid bound to phosphatidylcholine between Days 7 and 15 of the oestrous cycle. Less than 0\m=.\1% of the uterine arachidonic acid was present in the unesterified form. It is suggested that phosphatidylcholine may form the source of phosphatidyl for uterine prostaglandin synthesis in the guinea-pig.

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Levels of progesterone, prostaglandin F2alpha (PGF2alpha) and oestradiol in the utero-ovarian venous plasma of non-pregnant and early, unilaterally pregnant guinea-pigs were compared. Progesterone levels fell from day 12 to day 15 in the non-pregnant animals, while levels of PGF2alpha and oestradiol increased during this period. In contrast, in the pregnant guinea-pigs, progesterone levels remained high up to day 15 and PGF2alpha and oestradiol levels remained low in plasma from both the pregnant and non-pregnant sides. These findings support the hypothesis that the guinea-pig conceptus secretes an anti-luteolytic factor in early pregnancy, which reduces the amount of PGF2alpha produced by the uterus and released into the uterine veins and thereby allows luteal maintenance and continued progesterone secretion. Oestradiol, in the presence of progesterone, is regarded as the physiological stimulus for normal uterine PGF2alpha synthesis and release. Consequently, the inhibition of ovarian oestradiol secretion seen in early pregnancy is probably at least part of the mechanism by which the anti-luteolytic factor produced by the conceptus reduces PGF2alpha synthesis by and release from the uterus.

The supply of free arachidonic acid from phospholipids is generally regarded as the rate-limiting step for prostaglandin (PG) synthesis by tissues. Two enzymes involved in arachidonic acid uptake into, and release from, phospholipids are acyl-CoA:lysophospholipid acyltransferase (ACLAT) and phospholipase A2 (PLA2), respectively. PGF2 alpha produced by the endometrium induces luteolysis in several species including guinea-pigs. Thimerosal, an inhibitor of ACLAT, and aristolochic acid, an inhibitor of PLA2, both reduced, in a concentration-dependent manner, the output of PGF2 alpha from guinea-pig endometrium cultured for 24 h on days 7 and 15 of the oestrous cycle. This study showed that the continual production of PGF 2 alpha by guinea-pig endometrium is not only dependent upon the activity of PLA2 for releasing free arachidonic acid for PGF2 alpha synthesis, but also on the incorporation of arachidonic acid into the phospholipid pool by the activity of ACLAT. The inhibitory effects of thimerosal and aristolochic acid on the outputs of PGE2 and 6-keto-PGF1 alpha were less marked, particularly on day 7 when the low output of PGE2 was unaffected and the output of 6-keto-PGF1 alpha was increased at the lower concentrations of thimerosal. This finding indicates that there are different pools of arachidonic acid bound as phospholipid for the syntheses of PGF2 alpha and 6-keto-PGF1 alpha by guinea-pig endometrium.

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