ATP stimulates human placental 11β‐hydroxysteroid dehydrogenase type 2 activity by a novel mechanism independent of phosphorylation
Bibliographic record
Abstract
The human placental 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) is believed to play a key role in fetal development since this enzyme protects the fetus from exposure to high levels of maternal cortisol by virtue of converting maternal cortisol to its inert metabolite cortisone. The present study was undertaken to examine the effect of ATP on 11beta-HSD2 activity in human placental microsomes. Enzyme activity, reflected by the rate of conversion of cortisol to cortisone, was stimulated more than six-fold by 0.5 mM ATP (EC(50) = 0.2 mM). Such stimulation appears to be mediated through a novel mechanism independent of ATP-induced phosphorylation of the reaction components since AMP-PNP, a non-hydrolyzable analogue of ATP, was equally effective. The ATP-induced stimulation of 11beta-HSD2 activity is adenine nucleotide specific in that a similar stimulation was observed with ADP and AMP but not with CTP, GTP, or UTP. Furthermore, ATP increased the maximal velocity (V(max)) of the 11beta-HSD2 catalyzed conversion of cortisol to cortisone without altering the apparent K(m) of 11beta-HSD2 for cortisol, suggesting that ATP may stimulate enzyme activity by interacting with the enzyme at a site other than that involved in substrate binding. In conclusion, the present study has identified ATP as a novel regulator of human placental 11beta-HSD2 in vitro. It is conceivable that intracellular ATP may have a profound effect on 11beta-HSD2 function in vivo.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 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".