Physiological testosterone stimulates tissue plasminogen activator and tissue factor pathway inhibitor and inhibits plasminogen activator inhibitor type 1 release in endothelial cellsThis paper is one of a selection of papers in this Special Issue, entitled International Symposium on Recent Advances in Molecular, Clinical, and Social Medicine, and has undergone the Journal's usual peer-review process.
Bibliographic record
Abstract
There is a striking gender difference in atherosclerotic vascular disease. For decades, testosterone was considered detrimental to the cardiovascular system. Recent studies, however, have presented some alternative results. The aim of this study was to evaluate the effect of testosterone, using physiological and supraphysiological concentrations, on antigen and mRNA levels of tissue plasminogen activator (tPA), plasminogen activator inhibitor type 1 (PAI-1), and tissue factor pathway inhibitor (TFPI) released by human umbilical vein endothelial cells and to investigate the cellular mechanism. Cells within 2-3 passages were cultured in 25 cm(2) flasks or plated onto 96-well plates with a density of about 1 x 10(5) cells/mL as recommended. The cells were incubated in the presence or absence of testosterone (3, 30, 3 x 10(3), 3 x 10(4) nmol/L) for 48 h. Levels of tPA, PAI-1, and TFPI antigen were assayed with ELISA kits. Reverse transcriptase PCR was carried out to detect tPA, PAI-1, and TFPI mRNA levels. Cells were incubated in androgen-receptor antagonist (flutamide 10 micromol/L) or aromatase inhibitor (aminoglutethimide 50 micromol/L) for 3 h, and then the experiments were repeated. Testosterone at a physiologic concentration (30 nmol/L) increased the antigen levels of tPA and TFPI significantly (P < 0.05). However, tPA and TFPI levels were markedly reduced (P < 0.05) at a larger dose (3 x 10(4) nmol/L). On the other hand, PAI-1 antigen levels decreased significantly at the testosterone concentrations ranging from 3 to 3 x 10(4) nmol/L (P < 0.05). The change in the levels of tPA and TFPI were reflected in the corresponding change in mRNA levels. Flutamide attenuated the effect of testosterone at physiological concentration (30 nmol/L). The results demonstrated that testosterone at physiological concentrations may have a beneficial influence on the haemostatic system through enhancement of anticoagulant activity, resulting from stimulation of TFPI and tPA expression and inhibition of PAI-1 secretion by the endothelium.
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| 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".