1,25-Dihydroxyvitamin D3 Regulates Expression of Sex Steroid Receptors in Human Uterine Fibroid Cells
Bibliographic record
Abstract
CONTEXT: Uterine fibroids (UFs) are the most common benign tumors in premenopausal women. In this study, we evaluated the effects of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] for the treatment of UFs. OBJECTIVE: To determine the role of 1,25(OH)2D3 on the expression of sex steroid receptors in human UF cells. DESIGN: Human UFs and their adjacent myometrium were analyzed for expression of estrogen receptor (ER)-α, progesterone receptor (PR)-A, and PR-B, as well as members of the steroid receptor coactivator (SRC) family. Immortalized human uterine fibroid (human uterine leiomyoma [HuLM]) cells were treated with 1,25(OH)2D3 and assayed for the expression and localization of the aforementioned receptors and SRCs using Western blot, immunohistochemistry, immunofluorescence, and immunoprecipitation assays. MAIN OUTCOME MEASURES: We discovered a correlation between reduced levels of vitamin D receptor (VDR) and increased levels of ER-α, PR-A, and PR-B in these tissues. We evaluated the effects of 1,25(OH)2D3 on the regulation of the aforementioned sex steroid receptors. RESULTS: We observed an inverse correlation between the up-regulated ER-α, PR-A, and PR-B and expression of VDR in UFs. Treatment with 1,25(OH)2D3 significantly decreased levels of ER-α, PR-A, and PR-B, as well as SRCs in HuLM cells (P < .05). In contrast, 1,25(OH)2D3 self-induced its own VDR, which resulted in an induction of VDR-retinoid X receptor-α complex in HuLM cells. Together, these results suggest that 1,25(OH)2D3 functions as an antagonist of sex steroid hormone receptors in HuLM cells. CONCLUSIONS: 1,25(OH)2D3 functions as a potent antiestrogenic/antiprogesteronic agent that may have utility as a novel therapeutic option for UF.
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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 | 0.002 | 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 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".