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Record W2398323469 · doi:10.1038/ncomms11565

Molecular evidence of functional progesterone withdrawal in human myometrium

2016· article· en· W2398323469 on OpenAlex

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.
fundA Canadian funder is recorded on the work.

Bibliographic record

VenueNature Communications · 2016
Typearticle
Languageen
FieldMedicine
TopicPreterm Birth and Chorioamnionitis
Canadian institutionsUniversity of British ColumbiaUniversity of TorontoLunenfeld-Tanenbaum Research InstituteMount Sinai Hospital
FundersEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentCanadian Institutes of Health Research
KeywordsProgesterone receptorMyometriumNuclear receptorEndocrinologyInternal medicineReceptorProgestogenChemistryBiologyHormoneTranscription factorGeneMedicineUterusBiochemistry

Abstract

fetched live from OpenAlex

Progesterone suppresses uterine contractility acting through its receptors (PRA/B). The mechanism by which human labour is initiated in the presence of elevated circulating progesterone has remained an enigma since Csapo first theorized of a functional withdrawal of progesterone in 1965. Here we report that in vitro progesterone-liganded nuclear PRB forms a complex including JUN/JUN homodimers and P54(nrb)/Sin3A/HDAC to repress transcription of the key labour gene, Cx43. In contrast, unliganded PRA paradoxically activates Cx43 transcription by interacting with FRA2/JUND heterodimers. Furthermore, we find that while nuclear progesterone receptor (PR) is liganded during human pregnancy, it becomes unliganded during both term and preterm labour as a result of increased expression of the progesterone-metabolizing enzyme 20α HSD and reduced nuclear progesterone levels. Our data provide a mechanism by which human labour can occur in the presence of elevated circulating progesterone and suggests non-metabolizable progestogen might represent an alternative new therapeutic approach to preterm birth prevention.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

Full frame distilled prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.591
Threshold uncertainty score0.220

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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.

Opus teacher head0.032
GPT teacher head0.328
Teacher spread0.297 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it