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Prostaglandin biosynthesis was studied in the rat uterus during the oestrous cycle. Uterine homogenates were incubated for 20 minutes inthe presence of exogenous substrate (2.10(-5)M). PGF2 alpha and PGE2 were measured by R.I.A.. A sharp peak of PGF2 alpha and a smaller peak of PGE2 were observed at prooestrus, 20 h. Another small PGE2 peak occurred at dioestrus II, 15 h. The lowest values of both PGs were found on dioestrus, 15 h. Plasma oestradiol concentrations were highest at proestrus, 15 h and 20 h. A sharp progesterone peak occurred at prooestrus, 20 h. The PGF2 alpha peak is next to the oestradiol peak and is superimposable or lags slightly beyond the progesterone peak. Incubation with 14C arachidonic acid and subsequent analysis of extracts by TLC and scanning showed that the major metabolite is PGI2, identified as 6 keto PGF1 alpha. The conversion rate of arachidonic acid into 6 keto PGF1 alpha is 5 times higher than into PGF2 alpha. 6 Keto PGF1 alpha was further identified by GC/MS. No significant difference was observed between 6 keto PGF1 alpha production during oestrus and dioestrus.

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).

In vitro prostaglandin biosynthesis by uteri of ovariectomized rats and guinea pigs treated or untreated with oestradiol 17 beta, administered subcutaneously, was measured by R.I.A. of PGF2 alpha and PGE2. Incubations with [1-14C] arachidonic acid were also performed and labelled metabolites were analyzed by TLC. The main metabolite in rats was 6 keto PGF1 alpha and in decreasing order of magnitude, PGF2 alpha and PGE2. In guinea pig PGF2 alpha was the main product. Ovariectomy in rats completely changed the pattern of synthetized prostanoids : PGI2 production was doubled when compared to cycling rats and PGE2 increased 10 fold. PGF2 alpha values were similar to the mean value measured during the cycle. OE2 treatment almost completely inhibited PGI2 synthesis and reduced PGE2 by half. Total PG synthesis in OE2 treated animals was decreased by 5 fold when compared to spayed rats. Endogenous PGF2 alpha synthesis was slightly stimulated. In the guinea pig OE2 treatment of ovariectomized animals increased the total synthesis from 50 per cent. PGF2 alpha was always the main metabolite. In conclusion OE2 regulation of uterine PG synthesis is depending on the animal species and cannot be explained by a unique effect on the cyclooxygenase, but rather by an interplay on the various enzymes of the arachidonic acid cascade.