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17 beta-estradiol and progesterone were administered to post-menopausal women to determine their effects in vivo on the capacity of human endometrium to synthesize prostaglandins (PGs) F2 alpha and E. Basal amounts of PGF2 alpha and PGE synthesized by endometrium exposed to 17 beta-estradiol and progesterone were significantly higher than the levels produced by endometrium exposed to 17 beta-estradiol alone (p less than 0.02 for both PGs). Levels found in the former endometrium were broadly comparable to levels in secretory endometrium and in the latter to amounts found in proliferative endometrium of spontaneous, ovulatory cycles.

Concentrations of prostaglandin F2 alpha (PGF2 alpha) and prostaglandin E (PGE) were measured in endometrium from 18 women with ectopic pregnancies. In the nine pregnancies not associated with vaginal bleeding or an intra-uterine contraceptive device (IUCD; intact ectopics), concentrations of PGF2 alpha (12.8 +/- 7.4 (S.E.M.) ng/g) and PGE (4.7 +/- 3.0 ng/g) were similar to those in decidua from nine intra-uterine pregnancies of comparable gestational age (14.4 +/- 4.4 and 8.2 +/- 2.2 ng/g respectively). In both ectopic and intra-uterine pregnancies concentrations of prostaglandins were significantly lower than those found in endometrium throughout the normal menstrual cycle (P < 0.01). In nine ectopic pregnancies with associated vaginal bleeding and/or an IUCD, concentrations of PGF2 alpha and PGE were significantly higher than in the intact group (P < 0.05), although the concentration of PGF2 alpha remained significantly lower than levels in normal secretory endometrium (P < 0.05). These results suggested that suppression of endometrial synsthesis of prostaglandin during early pregnancy may be mediated systemically rather than through a local action of the conceptus.

Prostaglandins (PGs) have often been cited as intermediates in the action of the inert and copper-bearing intrauterine contraceptive device (IUD). Although investigations have shown an effect of copper at high (approx. 1 x 10(-4) mol/l) concentrations on PG synthesis, little consideration has been given to the possible effects of copper on PG metabolism. In this study the effect of copper and zinc ions on PG metabolism by human endometrium and myometrium has been investigated using radiolabel techniques together with gas chromatography mass spectrometry (GCMS) measurements of metabolites of PGE2. These experiments showed that concentration of 1 X 10(-5) mol/l of copper and zinc were sufficient to inhibit significantly (P less than 0.01) PGE metabolism. These levels of copper are within the physiological range of levels thought to be present in the uterine tissue and fluid of wearers of the copper-containing IUD and the inhibition of PG metabolism in these women might account for the small but significant decrease in the length of the luteal phase of their menstrual cycles.

We investigated the ability of the nonpregnant human uterus to metabolize prostaglandins E2 and F2 alpha (PGE2 and PGF2 alpha) using radiolabeled substrates together with gas chromatography-mass spectrometry for the measurement of specific metabolites. Both the 15-hydroxyprostaglandin dehydrogenase and the delta 13-reductase enzymes are present in endometrium and myometrium. As shown for other tissues, the dehydrogenase is NAD+ dependent, while the delta 13-reductase requires NADPH as cofactor. PGE2 was the preferred substrate in both tissues; however, the metabolizing capacity of follicular phase myometrium was comparable with that of midluteal phase endometrium. The Km values of the dehydrogenase for PGE2 and PGF2 alpha were similar in both endometrium (1.89 X 10(-6) and 18.52 X 10(-6) mol/liter, respectively) and myometrium (2.76 X 10(-6) and 11.64 X 10(-6) mol/liter, respectively), suggesting that the same enzyme is present in both tissues although the regulation of this enzyme may differ in endometrium and myometrium.

The endogenous concentrations of prostaglandins F2 alpha (PGF 2 alpha) and E (PGE) were measured during the luteal phase of the menstrual cycle in the endometrium from 14 women with unexplained menorrhagia (measured menstrual blood loss in excess of 50 ml) and 15 women with normal menses (blood loss 50 ml or less). Although there was no significant difference in the PGF 2 alpha/PGE ratio between the two groups, this ratio was significantly lower in the endometrium from eight of the women whose blood loss exceeded 90 ml (p less than 0.05). There was a significant inverse correlation between the PGF 2 alpha/PGE ratio and blood loss (r = 0.36, p less than 0.025). The synthetic capacity of the endometrium was assessed by incubation of the tissue with 14C arachidonic acid. Endometria from nine women with unexplained menorrhagia synthesized more PGE2 than PGF 2 alpha, whereas the converse was true with 11 control endometria. Consequently the PGF2 alpha/PGE2 ratio was significantly reduced in the former group (p less than 0.025). Oestradiol-17 beta (200 microM) and to a greater extent 2 hydroxy oestradiol (200 microM) increased the total prostaglandin synthesis by the endometria, but did not significantly alter the PGF2 alpha/PGE2 ratio. These results suggest that excessive blood loss may be associated with a shift in the endometrial conversion of prostaglandin endoperoxide from PGF2 alpha to PGE2.

The ability of broken cell preparations of human endometrium, myometrium and a mixture of endometrium and myometrium to convert 14C arachidonic acid to prostaglandins (PG's) was compared. Endometrium metabolished arachidonic acid predominantly to a mixture of PGF2 alpha and PGE2. A similar weight of myometrium showed relatively little activity, the major product identified was 6 oxo PGF1 alpha. However, a combination of endometrium and myometrium showed an enhanced conversion of arachidonic acid to 6 oxo PGF1 alpha associated with a decreased production of PGF2 alpha and PGE2. This suggests that human endometrium and myometrium differ in their ability to metabolize arachidonic acid and in their ability to convert the endoperoxides formed, to PG's.