Stimulation by human chorionic gonadotropin of prostaglandin synthesis by early human placental tissue.
Successful establishment of pregnancy is dependent on inhibition of clotting and suppression of the maternal immune response at the feto-maternal interface. Early human placental production of prostacyclin (PGI2) and prostaglandin E2 (PGE2) may be important in this process. To examine the possible role of these PGs, we studied PGE and 6-keto-PGF1 alpha (stable metabolite of PGI2) synthesis in human placental (9-17 weeks gestation) organ cultures, and monolayer cultures of purified trophoblasts. PGE2 appeared to be the major protanoid formed. Other arachidonic acid metabolites identified in placental organ culture were 6-keto-PGF1 alpha, thromboxane B2, PGF2 alpha, leukotriene B4, 5(S)-hydroxyeicosatetraenoic acid (5-HETE), 12-HETE, and 15-HETE. The synthesis of PGE and 6-keto-PGF1 alpha altered with gestation and was maximal in the younger placentas. Arachidonic acid (33 microM) stimulated and indomethacin (28 microM) inhibited PG production. hCG, including physiological concentrations, stimulated PGE and 6-keto-PGF1 alpha synthesis in placental organ cultures. This effect was most striking in the 9-12 week placentas, compared to 15-17 week placentas. A similar hCG-induced stimulation of PGE production occurred in monolayer cultures of trophoblasts. The addition of TSH, FSH, and LH indicated that this effect was specific for hCG. These data suggest that hCG may have a biological role in the regulation of PG synthesis in early human placenta.
North
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Department of Medicine, University of Melbourne, Royal Melbourne Hospital, Parkville, Victoria, Australia.
Whitehead
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Larkins
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D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D011464:Epoprostenol / Q000096:biosynthesis; D005260:Female; D005865:Gestational Age; D006801:Humans; D007700:Kinetics; D009924:Organ Culture Techniques; D010920:Placenta / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D011453:Prostaglandins / Q000096:biosynthesis*; D011458:Prostaglandins E / Q000096:biosynthesis; D014327:Trophoblasts / Q000378:metabolism
D001095:Arachidonic Acids; D006063:Chorionic Gonadotropin; D011453:Prostaglandins; D011458:Prostaglandins E; D016718:Arachidonic Acid; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol