Prostaglandin E2 metabolism in the human fetal membranes.
Prostaglandins play a pivotal role in the initiation and maintenance of labor, but the sources that contribute to the production of primary prostaglandins (prostaglandin E2 and prostaglandin F2 alpha) remain controversial. In decidua, prostaglandin F2 alpha may be formed de novo or from prostaglandin E2 through 9-ketoreductase activity, although it has been suggested that metabolism to 13,14-dihydro-15-ketoprostaglandin E2 through 15-hydroxyprostaglandin dehydrogenase is dominant. To examine this possibility, and to determine changes with labor, we examined interconversions of prostaglandin E2 to prostaglandin F2 alpha, 13,14-dihydro-15-ketoprostaglandin E2 and 13,14-dihydro-15-ketoprostaglandin F2 alpha by dispersed cells of decidua, chorion, and amnion obtained from patients at term elective cesarean section or after spontaneous labor. Incubations were performed with increasing concentrations (1 to 100 ng/ml) of prostaglandin E2 for 2 and 4 hours, and products were measured by radioimmunoassay. The 13,14-dihydro-15-ketoprostaglandin E2 was measured as 11-deoxy-13,14-dihydro-15-keto-11 beta, 16 psi-cycloprostaglandin E2. Basal output of prostaglandin E2 increased between cesarean section and spontaneous labor from 190.6 +/- 109 pg/10(5) cells (+/- SE) to 605.2 +/- 346.8 in amnion, nondetectable to 24.5 +/- 11.2 in chorion, and 18 +/- 16 to 69 +/- 25.8 in decidua. For both cesarean section and spontaneous labor patients there was very little conversion of prostaglandin E2 by the amnion, substantial conversion to 13,14-dihydro-15-ketoprostaglandin E2 by the chorion, and some conversion to 13,14-dihydro-15-ketoprostaglandin E2 by the decidua. Percentage conversions did not change with labor. Prostaglandin F2 alpha was formed by all tissues but only in trace amounts. All tissues from one cesarean section patient showed substantial conversion of prostaglandin E2 to prostaglandin F2 alpha, but very little 13,14-dihydro-15-ketoprostaglandin E2 or 13,14-dihydro-15-ketoprostaglandin F2 alpha formation, indicating either a decrease or deficiency in the 15-hydroxyprostaglandin dehydrogenase activity. We conclude that conversion of exogenous prostaglandin E2 to prostaglandin F2 alpha can occur in intrauterine tissues, but this does not normally contribute significantly to the prostaglandin F2 alpha output by the human decidua and fetal membranes.
Cheung
P Y
PY
Department of Obstetrics and Gynecology, University of Western Ontario, London, Ontario, Canada.
Challis
J R
JR
D000650:Amnion / Q000166:cytology / Q000378:metabolism; D002469:Cell Separation; D002823:Chorion / Q000166:cytology / Q000378:metabolism; D003656:Decidua / Q000166:cytology / Q000378:metabolism; D015237:Dinoprost / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism* / Q000494:pharmacology; D005321:Extraembryonic Membranes / Q000166:cytology / Q000378:metabolism*; D005260:Female; D006801:Humans; D011247:Pregnancy
D015237:Dinoprost; D015232:Dinoprostone