Glucocorticoids stimulate prostaglandin synthesis in human amnion cells by a receptor-mediated mechanism.
Prostaglandin E2 (PGE2) synthesis by human amnion increases with the onset of labor and is thought to participate in the initiation and maintenance of parturition. Since cortisol levels increase in amniotic fluid in late pregnancy, we studied the effects of glucocorticoids on cultured term human amnion cell PGE2 output. In 24-h studies, the synthetic glucocorticoid dexamethasone stimulated basal PGE2 output 2-fold over control levels at 16-500 nmol/L. PGE2 output was dramatically stimulated (greater than 10-fold) when, after dexamethasone pretreatment, the cells were incubated with calcium ionophore A23187 or arachidonic acid (AA) for 2 h. Maximum effects were achieved at 31 nmol/L dexamethasone. Basal PGE2 output was stimulated at 12 h of dexamethasone treatment, whereas A23187- or AA-stimulated PGE2 output was enhanced after 3-6 h of dexamethasone pretreatment. Cortisol (50 and 500 nmol/L) also enhanced basal and stimulated PGE2 output, while dehydroepiandrosterone sulfate, 17 beta-estradiol, and progesterone were ineffective. The glucocorticoid receptor antagonist RU 38486 attenuated dexamethasone-enhanced basal and stimulated PGE2 output. Dexamethasone pretreatment had no effect on basal or stimulated PGE2 output from cultured term chorion cells, suggesting tissue specificity. We conclude that glucocorticoids specifically enhance PGE2 output from cultured amnion cells via a receptor-mediated mechanism. We speculate that the action of glucocorticoids is to increase the capacity of the cells to convert AA to PGE2.
D000650:Amnion / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002478:Cells, Cultured; D002823:Chorion / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D003907:Dexamethasone / Q000037:antagonists & inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis*; D004963:Estrenes / Q000494:pharmacology; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D015735:Mifepristone; D011247:Pregnancy; D011965:Receptors, Glucocorticoid / Q000502:physiology*
D001095:Arachidonic Acids; D004963:Estrenes; D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D016718:Arachidonic Acid; D015735:Mifepristone; D000001:Calcimycin; D003907:Dexamethasone; D015232:Dinoprostone