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.
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Patel FA, Funder JW, Challis JR
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.
J Clin Endocrinol Metab. 2003 Jun;88(6):2922-33.
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- 12788907 [ View in PubMed]
- Abstract
Prostaglandin dehydrogenase (PGDH) metabolizes prostaglandins (PGs) to render them inactive. We reported previously that cortisol (F) decreases and progesterone (P(4)) maintains PGDH activity/expression in human chorion and placenta. Furthermore, we have shown that F and P(4) compete for regulation of PGDH. We hypothesized that P(4) maintains PGDH activity through interaction with the glucocorticoid receptor (GR) and that elevations in F compete with P(4) 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), beta-methasone, P(4), trilostane (a 3 beta-hydroxysteroid dehydrogenase inhibitor), medroxyprogesterone acetate (MPA), and/or 21-hydroxy-6,19-oxidopregn-4-ene-3,20-dione (21OH-6OP; 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 P(4), treatment stimulated PGDH activity. Trilostane inhibited PGDH activity, and coincubation with P(4) or MPA reversed trilostane inhibition of PGDH. Treatment with trilostane, P(4), 21OH-6OP, or MPA plus 21OH-6OP reversed P(4) and MPA up-regulation of PGDH activity. Our findings suggest that F inhibition and P(4) stimulation of PGDH may be mediated by PR, but also via the GR, in chorion and placenta.