ArticleThe Journal of clinical endocrinology and metabolism2008
Retinoic acid (RA) regulates 17beta-hydroxysteroid dehydrogenase type 2 expression in endometrium: interaction of RA receptors with specificity protein (SP) 1/SP3 for estradiol metabolism.
Article in The Journal of clinical endocrinology and metabolism, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 68 citations in OpenAlex.
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- Activation of Genes by Nuclear Receptor/Specificity Protein (Sp) Interactions in Cancer.Cancers · 2025Review
- Vitamins in Gynecologic Malignancies.Nutrients · 2024Review
- Horizons in Endometriosis: Proceedings of the Montreux Reproductive Summit, 14-15 July 2023.Facts, views & vision in ObGyn · 2024Article
- In-depth proteome characterization of endometrium and extraembryonic membranes during implantation in pig.Journal of animal science and biotechnology · 2024Article
- Pattern-recognition receptors in endometriosis: A narrative review.Frontiers in immunology · 2023Review
- Role of adipokines in embryo implantation.Endocrine connections · 2021Review
- Selective Progesterone Receptor Modulators-Mechanisms and Therapeutic Utility.Endocrine reviews · 2020Review
- Influence of breast cancer risk factors and intramammary biotransformation on estrogen homeostasis in the human breast.Archives of toxicology · 2020Article
- Genetic, Epigenetic, and Steroidogenic Modulation Mechanisms in Endometriosis.Journal of clinical medicine · 2020Review
- Endometriosis.Endocrine reviews · 2019Review
- Endometriosis and nuclear receptors.Human reproduction update · 2019Review
- Article
- Fenretinide: A Potential Treatment for Endometriosis.Reproductive sciences (Thousand Oaks, Calif.) · 2016Article
- Moving Toward Integrating Gene Expression Profiling Into High-Throughput Testing: A Gene Expression Biomarker Accurately Predicts Estrogen Receptor α Modulation in a Microarray Compendium.Toxicological sciences : an official journal of the Society of Toxicology · 2016Article
- Article
- Article
- All-trans retinoic acid up-regulates the human CD2AP gene expression through Sp1/Sp3 binding sites.Immunologic research · 2015Article
- Fenretinide: a novel treatment for endometrial cancer.PloS one · 2014Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
contextThe enzyme 17beta-hydroxysteroid dehydrogenase type 2 (HSD17B2) exerts a local antiestrogenic effect by metabolizing biologically active estradiol to inactive estrone in endometrial epithelial cells. Retinoic acid (RA) induces HSD17B2 expression, but the underlying mechanism is not known.
objectiveOur objective was to elucidate the molecular mechanisms responsible for HSD17B2 expression in human endometrial cells.
methodHuman endometrial Ishikawa and RL95-2 cell lines were cultured in the presence or absence of RA to analyze endogenous HSD17B2 expression, transcription factor complex formation, and promoter activity.
resultsRA induced HSD17B2 mRNA levels in a dose- and time-dependent manner in endometrial cells. The RA antagonist ANG11273 abolished RA-induced HSD17B2 expression. Small interfering RNA ablation of RA receptor (RAR)alpha or retinoid X receptor (RXR)alpha completely blocked RA-induced HSD17B2 gene expression. Analysis of serial deletion and site-directed mutants of the HSD17B2 promoter fused to a reporter gene indicated that RA induction requires a cis-regulatory sequence that binds the specificity protein (SP) class of transcription factors. Chromatin-immunoprecipitation-PCR and gel-shift assays showed that RARalpha/RXRalpha and SP1/SP3 interact with this HSD17B2 promoter sequence. Small interfering RNA ablation of SP1 and SP3 expression markedly decreased HSD17B2 basal expression and blocked RA-induced expression. Finally, immunoprecipitationimmunoblotting demonstrated RA-induced interactions between RARalpha/RXRalpha and SP1/SP3 in intact endometrial cells.
conclusionsIn endometrial epithelial cells, RA stimulates formation of a multimeric complex comprised of RARalpha/RXRalpha tethered to transcription factors SP1 and SP3 on the HSD17B2 promoter. Assembly of this transcriptional complex is necessary for RA induction of HSD17B2 expression and may be an important mechanism for local estradiol inactivation in the endometrium.
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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.