The Multidrug Resistance-Associated Protein 4 (MRP4) Appears as a Functional Carrier of Prostaglandins Regulated by Oxytocin in the Bovine Endometrium
Bibliographic record
Abstract
Prostaglandins (PG) are involved in several female reproductive processes, and their action is regulated at the levels of biosynthesis, catabolism, and signal transduction. Facilitated transport across cell membranes emerges as an additional checkpoint regulating PG action. We have already reported on the influx transporter solute carrier organic anion transporting polypeptide (SLCO2A1) [PG transporter (PGT)] in relation to PG action in the bovine endometrium. In the present study, we report on the functional expression and regulation of multidrug resistance-associated protein 4 (MRP4)/ATP-binding cassette carrier 4, an alternate PG transporter belonging to the ATP-binding cassette carrier (ABC) family. We have found that MRP4 protein was present throughout the estrous cycle and exhibited a pattern of expression similar to that of PGT with maximal expression during early-mid luteal phase in the bovine endometrium. Functional expression and regulation of MRP4 was studied in vitro using the newly developed bovine endometrial epithelial bEEL and stromal CSC cell lines. Oxytocin (OT) stimulated PGF2α production and MRP4 mRNA and protein in a time- and dose-dependent manner but had no effect on PGT. OT induced preferred accumulation of PG outside the cells and secretion toward the basolateral side of polarized bEEL cells grown on membrane inserts. MK-571 and indomethacin, two documented inhibitors of MRP4 activity, blocked preferred accumulation of PG, but interferon-τ and NS-398 had no effect on MRP4 expression or the direction of PG transport. Our results suggest that MRP4 is a functional PG carrier under the regulation of OT in the bovine endometrium.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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".