Complex Regulatory Effects of Gonadal Steroids on the Expression Levels of the Distinct Aggrecanases Present in Human Endometrial Stromal Cells In Vitro.
Bibliographic record
Abstract
The ADAMTS (A Disintegrin And Metalloproteinase with ThromboSpondin repeats) are a novel gene superfamily of metalloproteinases composed of at least 20 genetically distinct members. Of these, ADAMTS-1, -4, -5, -8, -9 and -15 have been further subclassified into a subfamily, known as the aggrecanases, owing to their ability to cleave large chondroitin sulphates in the extracellular matrix, a key cellular event underlying tissue remodeling under normal and pathological conditions. We have recently determined that two members of this ADAMTS subfamily, ADAMTS-1 and -5, are spatiotemporally expressed in the human endometrium during the menstrual cycle and that progesterone (P4) and the non-aromatisable androgen, dihydrotestosterone (DHT) but not 17 beta-estradiol (E2) increased ADAMTS-1 expression levels in primary cultures of human endometrial stromal cells. In these studies, we have further characterized the repertoire of aggrecanases present in primary cultures of human endometrial stromal cells and examined the ability of gonadal steriods to regulate the expression levels of these distinct ADAMTS subtypes by using a real time PCR strategy and Western blot analysis. Here we report that in addition to ADAMTS-1 and -5, ADAMTS-4, -8, and -9 but not -15 are expressed in human endometrial stromal cell in vitro. P4 and DHT but not E2 significantly increased ADAMTS-8 and -9 mRNA and protein expression levels in these primary cell cultures in a concentration- and time-dependent manner. In contrast, DHT significantly decreased stromal ADAMTS-5 expression levels whereas ADAMTS-4 mRNA and protein levels remained relatively unchanged in all the primary cell cultures examined in these studies. We believe that these findings provide further evidence that aggrecanases contribute to the steroid-mediated ECM remodeling events that occur in the endometrium in preparation for pregnancy.These studies are funded by a grant from the Canadian Institutes of Health Research (CDM). JW is the recipient of a studentship from the Canadian Institutes of Health Research.
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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".