4-Hydroxytamoxifen Is an Isoform-Specific Inhibitor of Orphan Estrogen-Receptor-Related (ERR) Nuclear Receptors β and γ
Bibliographic record
Abstract
Selective estrogen receptor modulators (SERMs) are synthetic molecules that exhibit tissue-specific activities. 4-hydroxytamoxifen (OHT) is a first generation SERM that functions as an antagonist in breast cancer cells but displays estrogen-like activities in the uterus and bone. The estrogen-receptor-related receptors (ERR) alpha, beta and gamma are orphan members of the superfamily of nuclear receptors. While the ERRs do not respond to natural estrogens, these receptors recognize the estrogen response element and have been shown to activate and repress gene expression in the absence of exogenously added ligand. Here we show that OHT disrupts the interaction between the orphan estrogen-receptor-related (ERR) receptors beta and gamma and a coregulator protein and abolishes the constitutive transcriptional activity of these receptors in transient transfection assays. In contrast, OHT has no effect on coregulator/ERR alpha interaction or its transcriptional activity. These results demonstrate the existence of a novel nuclear receptor-based pharmacological pathway that may contribute to the tissue-specific activities of OHT.
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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".