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- Title
Mechanism of Cortisol/Progesterone Antagonism in the Regulation of 15-Hydroxyprostaglandin Dehydrogenase Activity and Messenger Ribonucleic Acid Levels in Human Chorion and Placental Trophoblast Cells at Term.
- Authors
PATEL, FALGUNI A.; FUNDER, JOHN W.; CHALLIS, JOHN R. G.
- Abstract
Prostaglandin dehydrogenase (PGDH) metabolizes prostaglandins (PGs) to render them inactive. We reported previously that cortisol (F) decreases and progesterone (P4) maintains PGDH activity/expression in human chorion and placenta. Furthermore, we have shown that F and P4 compete for regulation of PGDH. We hypothesized that P4 maintains PGDH activity through interaction with the glucocorticoid receptor (GR) and that elevations in F compete with P4 at the GR, resulting in a decrease in PGDH at term. By immunohistochemistry and Western blotting analysis, we localized immunoreactive GR and progesterone receptor (PR) to chorion and placental trophoblast cells. We treated chorion and placental trophoblast cells in culture with F, dexamethasone (DEX), β-methasone, P4, trilostane (a 3β-hydroxysteroid dehydrogenase inhibitor), medroxyprogesterone acetate (MPA), and/or 21-hydroxy-6,19-oxidopregn-4-ene-3,20-dione (21OH6OP; a GR antagonist). By RIA and Northern blotting analysis, all glucocorticoids (GCs) decreased PGDH activity/expression. Coincubation with 21OH-6OP reversed GC inhibition of PGDH; MPA, but not P4, treatment stimulated PGDH activity. Trilostane inhibited PGDH activity, and coincubation with P4 or MPA reversed trilostane inhibition of PGDH. Treatment with trilostane, P4, 21OH-6OP, or MPA plus 21OH-6OP reversed P4 and MPA up-regulation of PGDH activity. Our findings suggest that F inhibition and P4 stimulation of PGDH may be mediated by PR, but also via the GR, in chorion and placenta.
- Publication
Journal of Clinical Endocrinology & Metabolism, 2003, Vol 88, Issue 6, p2922
- ISSN
0021-972X
- Publication type
Article
- DOI
10.1210/jc.2002-021710