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
Bibliographic record
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.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".