Effect of toremifene and ospemifene, compared to acolbifene, on estrogen-sensitive parameters in rat and human uterine tissues
Bibliographic record
Abstract
BACKGROUND: Although the first generation selective estrogen receptor modulator (SERM) tamoxifen (TAM) is well known for its uterotrophic activity, this study compares the stimulatory effect of the TAM derivatives toremifene (TORE) and ospemifene (OSPE) on estrogen-sensitive parameters in rat and human uterine tissues. MATERIAL AND METHODS: Ovariectomized female rats were treated daily orally for 10 days with 0.75 mg/rat of TORE, OSPE or acolbifene (ACOL, a pure estrogen antagonist in the uterus and mammary gland), which was used for comparison. Human endometrial carcinoma Ishikawa cells were incubated for 5 days with increasing doses of compounds, in the absence or presence of 1 nM estradiol (E2). RESULTS: TORE and OSPE revealed 52% and 56% increases, respectively, in uterine weight, whereas ACOL had no effect. Similar effects were observed on vaginal weight. Endometrial epithelial height increased from 15.82±0.20 to 48.94± 2.12 and 42.14±1.95 μm with TORE and OSPE, respectively, whereas ACOL had no effect. Alkaline phosphatase activity, an estrogen-sensitive parameter in Ishikawa cells, was increased by 144% and 135% with OH-TORE and OH-OSPE, respectively. Owing to their intrinsic estrogenic activity, at maximal concentrations, OH-TORE and OH-OSPE blocked the stimulatory effect of E2 by only 89% compared to 100% with ACOL. CONCLUSIONS: The present in vitro and in vivo data show similar stimulatory effects of 4-hydroxytoremifene (OH-TORE) and OH-OSPE on estrogen-sensitive parameters. ACOL, a third generation SERM, has no effect on any of these parameters. Such data add to the potential uterine safety limitations of triphenylethylene-derived SERMs for long-term use in humans.
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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) | 0.000 | 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".