Regulation of Calcium Transport Pathways in Kidney and Intestine During Lactation
Bibliographic record
Abstract
Significant alterations in maternal calcium balance occur postpartum during lactation. Demineralization of the skeleton mobilizes calcium, in order to supply this mineral to the neonate via breast milk. Changes in intestinal and renal calcium transport processes also promote this. However, the specific molecular alterations in transcellular and paracellular calcium transport pathways across renal and intestinal epithelia during lactation have not been fully delineated. To ascertain which changes occur during lactation, female mice were divided into 3 groups, non‐pregnant controls, lactating mice with litters maintained for 12 days after birth, or mice undergoing involution with litters removed after birth and maintained for 12 days. Induction of lactogenesis was confirmed histologically in mammary fat pads. Bodyweight increased in lactating mice as did urinary volume, measured during 9‐hr collections performed on day 11. Both total urinary excretion and fractional excretion of calcium and magnesium were elevated during lactation. Enlargement of the intestinal tract was confirmed visually in lactating animals. Renal 1‐alpha hydroxylase and 24‐OHase mRNA expression increased dramatically. This was accompanied by significant increases in the gene expression of Trpv6 and Calbindin‐D 9K in duodenum and proximal large bowel of lactating mice. No significant alterations in the calcium permeable claudins (−2, −12 or −15) were observed in any intestinal segments. A similar gene expression profile was observed in kidney, which showed no change in claudins (−2, −12, −14, −15, −16 or −19), while marked increases in Trpv5 and Calbindin‐D 28K were observed. Increased Calbindin‐D 28K protein expression was found by immunohistochemical analysis, while no changes in claudin‐2 were noted, in line with observations from mRNA expression analysis. In conclusion, proteins driving transcellular calcium transport pathways increase during lactation, likely due to increased Vitamin D dependent‐stimulation, while proteins mediating paracellular transport appear unchanged. Increased urinary mineral excretion can be explained on the basis of intestinal hyperabsorption and bone demineralization, although selective calcium uptake is maintained in kidney. Support or Funding Information This work was funded by grants from the Novo Nordisk Foundation (HD), the Carlsberg Foundation (HD), the A.P. Møller Foundation (HD), the Lundbeck foundation (HD), the Kidney Foundation of Canada (RTA), and the Canadian Institute of Health Research (CIHR) (RTA). A Clinician Scientist Award from CIHR and an Alberta Innovates Health Solutions Clinical Investigator Award supports Dr. R.T. Alexander.
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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 | 0.000 | 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) | 0.001 | 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 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".