Estradiol Inhibits Smooth Muscle Cell Growth in Part by Activating the cAMP-Adenosine Pathway
Bibliographic record
Abstract
Estradiol inhibits smooth muscle cell growth; however, the mechanisms involved remain unclear. Because estradiol stimulates cAMP synthesis and adenosine inhibits cell growth, we hypothesized that the conversion of cAMP to adenosine (ie, the cAMP-adenosine pathway) mediates in part the inhibitory effects of estradiol on vascular smooth muscle cell growth. To test this hypothesis, we examined the effects of estradiol (0.001 to 1 micromol/L) on serum-induced DNA, collagen, and total protein synthesis and cell number in the absence and presence of 1, 3-dipropyl-8-p-sulfophenylxanthine (10 nmol/L; A(1)/A(2) adenosine receptor antagonist), KF17837 (10 nmol/L; selective A(2) adenosine receptor antagonist), 8-cyclopentyl-1,3-dipropylxanthine (10 nmol/L; selective A(1) adenosine receptor antagonist), and 2', 5'-dideoxyadenosine (10 micromol/L; adenylyl cyclase inhibitor). Estradiol inhibited all measures of cell growth, and the concentration-dependent inhibitory curves for estradiol were shifted to the right (P<0.05) by 1,3-dipropyl-8-p-sulfophenylxanthine, KF17837, and 2',5'-dideoxyadenosine but not by 8-cyclopentyl-1, 3-dipropylxanthine. Moreover, the inhibitory effects of estradiol were enhanced by stimulation of adenylyl cyclase with forskolin and by inhibition of adenosine metabolism with erythro-9-(2-hydroxy-3-nonyl)adenine plus iodotubericidin (adenosine deaminase and kinase inhibitors, respectively). Estradiol also increased levels of cAMP and adenosine, and these effects were blocked by 2',5'-dideoxyadenosine (P<0.05). Our results support the hypothesis that estradiol stimulates cAMP synthesis and cAMP-derived adenosine regulates smooth muscle cell growth via A(2) adenosine receptors. Thus, the cAMP-adenosine pathway may contribute importantly to the antivasooclusive effects of estradiol.
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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".