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The Journal of Clinical Endocrinology & Metabolism Vol. 84, No. 2 395-400
Copyright © 1999 by The Endocrine Society

Original Studies

Local Modulation by 11ß-Hydroxysteroid Dehydrogenase of Glucocorticoid Effects on the Activity of 15-Hydroxyprostaglandin Dehydrogenase in Human Chorion and Placental Trophoblast Cells1

Falguni A. Patel, Kang Sun and John R. G. Challis

University of Toronto, Departments of Physiology (F.A.P., K.S., J.R.G.C.) and Obstetrics and Gynaecology (J.R.G.C.), Medical Research Council Group in Fetal and Neonatal Health and Development (J.R.G.C.), Samuel Lunenfeld Research Institute, Mount Sinai Hospital (J.R.G.C.), Toronto, Canada

Address all correspondence and requests for reprints to: Ms. Fal Patel, Department of Physiology, 3rd Floor, Medical Sciences Building, University of Toronto, 1 King’s College Circle, Toronto, Ontario M5S 1A8, Canada. E-mail: fal.patel{at}utoronto.ca

NAD+-dependent 15-hydroxy-PG dehydrogenase (PGDH) is the major enzyme involved in the initial inactivation of PGs, and its activity is reduced by glucocorticoids, cortisol (F), and dexamethasone (DEX). In turn, glucocorticoid regulation of PGDH activity in placenta and chorion could be regulated indirectly by 11ß-hydroxysteroid dehydrogenase (11ß-HSD) activity. In the placenta, 11ß-HSD2 is the dominant isoform, acting as a dehydrogenase [F to cortisone (E)]; and in chorion, 11ß-HSD1 predominates as a reductase (E to F). The present study was designed to determine whether glucocorticoid regulation of PGDH activity in placenta and chorion could be regulated indirectly by 11ß-HSD activity. We obtained Percoll-purified human placental and chorion trophoblast cells from uncomplicated term pregnancies, cultured them for 72 h, then treated the cells with cortisol (100 nmol/L), cortisone (1 µmol/L), or DEX (100 nmol/L), in the presence or absence of carbenoxolone (CBX, 800 nmol/L), an 11ß-HSD inhibitor, for 24 h. Activity of PGDH was assessed by incubation (4 h) with PGF2{alpha} (282 nmol/L) and measurement of conversion to 13,14-dihydro-15-keto PGF2{alpha}. CBX alone had no effect on PGDH activity in either placenta or chorion trophoblast cells. In chorion, E significantly inhibited PGDH activity, and this effect was reversed by addition of CBX. F and DEX significantly inhibited PGDH, and this effect was unaltered by coadministration of CBX. In contrast, in placenta, there was no effect of E, or of E with CBX, on PGDH activity. However, F and DEX inhibited PGDH, and the effect of F (but not DEX) was greater in the presence of CBX. In conclusion, we suggest that effects of E and F on PGDH are modified by the tissue-specific expression of 11ß-HSD isoforms.




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