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Glucocorticoids Stimulate Prostaglandin Synthesis In Human Amnion Cells by a Receptor-Mediated Mechanism^*

FRANK A. POTESTIO, TAMAS ZAKAR and DAVID M. OLSON

Departments of Pediatrics and Physiology, Lawson Research Institute, St. Joseph’s Health Centre of London, University of Western Ontario London, Ontario, Canada

Address all correspondence and requests for reprints to: David M. Olson, Ph.D., Lawson Research Institute, St. Joseph’s Health Centre of London, 268 Grosvenor Street, London, Ontario, Canada N6A 4V2.

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 (>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 β-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.

^* This work was supported by a March of Dimes-Birth Defects Foundation Basil O’Connor Starter Research Grant (5–530), the Medical Research Council of Canada, and the Department of Pediatrics, U.W.O.

Recipient of the Graduate Student Bursary (Department of Pediatrics).

Recipient of a Visiting Professorship (Lawson Research Institute). Permanent address: First Institute of Biochemistry, Semmelweis University Medical School, Budapest, Hungary.

Scholar of the MRC.

Received April 6, 1988.

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