Differential Effects of 1,25D3‐MARRS Expression on Mammary Gland Growth and Development Depend on the Vitamin D <sub>3</sub> Dose
Bibliographic record
Abstract
1,25 dihydroxyvitamin D 3 (1,25D3) is one of the most potent biologically active forms of vitamin D 3 . Primary activities include regulation of blood calcium and phosphate homeostasis and a plethora of other effects including cell growth inhibition, induction of differentiation, and anti‐cancer effects, depending on the target tissue. Most of the activities of 1,25D3 continue to be ascribed to the classic vitamin D receptor despite the identification of another membrane receptor for 1,25D3. The membrane‐associated rapid response steroid‐binding (MARRS) receptor is receiving more attention as a novel vitamin D receptor working through rapid, non‐genomic pathways. The purpose of this study was to explore the role of MARRS in the mammary gland using a conditional knockout mouse model and a vitamin D 3 dietary intervention. 1,25D3‐MARRS expression was reduced in epithelial cells of mammary glands (MG) using the Cre/loxp system. Dams were weaned onto semi‐purified diets with 10,000 IU/kg, 1,000 IU/kg, or 0 IU/kg of 1,25D3 for 4 weeks before being set‐up to breed. 4 th MGs were collected from 6‐week old female MMTV‐Cre mice (n=73). MGs were whole‐mounted and stained with carmine alum. Tissue growth was assessed by counting the number of terminal end buds (TEB) of alveolar branches, measuring the length of the longest ductal extension, and measuring total MG area covered ducts. Whole body weight was similar between all groups. There was a significant interaction between genotype and diet. Knockout mice on the 1,000 IU/kg diet had significantly fewer TEBs (p=0.016) and reduced ductal growth and extension (p=0.037, p=0.023 respectively) compared to controls on the same diet. Mice on the 0 IU/kg diet had similar TEB counts across all genotypes. Knockout mice on the 10,000IU/kg diet had significantly more TEBs than the other mice of the same diet (p=0.042), and more extensive growth and coverage of alveolar branches than knockouts on the 1,000 IU/kg diet. These results suggest that there is an effect of 1,25D3‐MARRS that is dependent on vitamin D 3 dose. Because the dose‐response is not linear in this animal model, it suggests caution when making recommendations for vitamin D 3 nutrition in animals, and possibly humans as well. Support or Funding Information The Natural Sciences and Engineering Research Council of Canada
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".