Evidence map›Paper›PMID 40290045›Full record

ArticleThe Journal of clinical endocrinology and metabolism2025

Increased HSD11β1 Expression in Human Leiomyomatous Uteri: Implication for Enhanced Glucocorticoid Signaling.

Carrie Malcom, Ozlem Guzeloglu-Kayisli, Burak Un, Erika New, Busra Cetinkaya-Un, Xiaofang Guo, Emad Mikhail, Anthony Imudia, Charles Lockwood, Umit Kayisli

Abstract read
In one paragraph

Article in The Journal of clinical endocrinology and metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Carrie MalcomDepartment of Obstetrics & Gynecology, University of South Florida, Morsani College of Medicine, Tampa, FL 33606, USA.ORCID 0009-0007-2939-8883
Ozlem Guzeloglu-KayisliDepartment of Obstetrics & Gynecology, University of South Florida, Morsani College of Medicine, Tampa, FL 33606, USA.
Burak UnDepartment of Obstetrics & Gynecology, University of South Florida, Morsani College of Medicine, Tampa, FL 33606, USA.
Erika NewDepartment of Obstetrics & Gynecology, University of South Florida, Morsani College of Medicine, Tampa, FL 33606, USA.
Busra Cetinkaya-UnDepartment of Obstetrics & Gynecology, University of South Florida, Morsani College of Medicine, Tampa, FL 33606, USA.
Xiaofang GuoDepartment of Obstetrics & Gynecology, University of South Florida, Morsani College of Medicine, Tampa, FL 33606, USA.
Emad MikhailDepartment of Obstetrics & Gynecology, University of South Florida, Morsani College of Medicine, Tampa, FL 33606, USA.
Anthony ImudiaDepartment of Obstetrics & Gynecology, University of South Florida, Morsani College of Medicine, Tampa, FL 33606, USA.
Charles LockwoodDepartment of Obstetrics & Gynecology, University of South Florida, Morsani College of Medicine, Tampa, FL 33606, USA.
Umit KayisliDepartment of Obstetrics & Gynecology, University of South Florida, Morsani College of Medicine, Tampa, FL 33606, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

contextFK506-binding-protein-51 (FKBP51) is a glucocorticoid-induced co-chaperone protein previously shown to bind glucocorticoid receptor (GR), inhibiting its transcriptional activity. We previously found increased FKBP51 levels in uterine leiomyoma vs paired myometrium.

objectiveTo test the hypothesis that elevated FKBP51 levels contribute to leiomyoma pathogenesis by altering GR signaling.

designRNA-sequencing was performed in leiomyoma cell cultures transfected with scramble or FKBP5-siRNA for 48 hours, then treated with vehicle or dexamethasone (DEX) for 24 hours. Differentially expressed genes, including HSD11B1, CNN1, and LAMA2 were analyzed by quantitative polymerase chain reaction. Hydroxysteroid 11-β dehydrogenase 1 (HSD11β1) expression was analyzed in leiomyoma, leiomyoma-adjacent paired myometrium, myometrium from patients without leiomyoma, and human endometrial stromal cells by quantitative polymerase chain reaction and immunohistochemistry.

settingUniversity research institution. PATIENTS: Women with or without uterine leiomyoma.

main outcome measuresHSD11B1 mRNA and protein levels in leiomyoma, paired myometrium, and normal myometrium.

resultsHSD11β1 expression was higher in paired myometrial and leiomyoma tissues vs normal myometrium (P < .02). DEX treatment increased HSD11B1 transcription in normal myometrial and human endometrial stromal cell cultures, but to a significantly greater extent in leiomyoma (P < .001). However, FKBP5-silencing blunted this DEX-induced HSD11B1 upregulation. DEX-treatment reduced LAMA2 and increased CNN1 levels (coding for extracellular matrix and smooth muscle proteins, respectively) in FKBP5-silenced vs scramble siRNA-transfected leiomyoma cultures.

conclusionFKBP51 not only inhibits but can augment GR-mediated transcription. Importantly, FKBP51-GR interactions increase HSD11B1 levels in leiomyoma cells, generating a pathological FKBP51-GR-HSD11β1 circle, altering transcription of downstream extracellular matrix and smooth muscle genes to induce a myofibroblast phenotype, thereby possibly contributing to leiomyoma pathogenesis.

Indexed as

11-beta-Hydroxysteroid Dehydrogenase Type 1GlucocorticoidsLeiomyomaUterine NeoplasmsAdultDexamethasoneFemaleGene Expression Regulation, NeoplasticHumansMiddle AgedMyometriumReceptors, GlucocorticoidSignal TransductionTacrolimus Binding Protein 5Tacrolimus Binding Proteins11-beta-Hydroxysteroid Dehydrogenase Type 1DexamethasoneGlucocorticoidsHSD11B1 protein, humanReceptors, GlucocorticoidTacrolimus Binding Protein 5Tacrolimus Binding ProteinsFKBP51gene expressionglucocorticoid signalingHSD11β1leiomyoma

Identifiers

PMID40290045
PMCPMC12623045

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.