Cited by 143Estrogen and related hormone effectsThyroid Disorders and TreatmentsEffects and risks of endocrine disrupting chemicals

Estrogen and thyroid hormone interaction on regulation of gene expression.

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Zhu, Y S, Yen, P M, Chin, W W, Pfaff, D W·1996·Proceedings of the National Academy of Sciences

Abstract

Estrogen receptor (ER) and thyroid hormone receptors (TRs) are ligand-dependent nuclear transcription factors that can bind to an identical half-site, AGGTCA, of their cognate hormone response elements. By in vitro transfection analysis in CV-1 cells, we show that estrogen induction of chloramphenicol acetyltransferase (CAT) activity in a construct containing a CAT reporter gene under the control of a minimal thymidine kinase (tk) promoter and a copy of the consensus ER response element was attenuated by cotransfection of TR alpha 1 plus triiodothyronine treatment. This inhibitory effect of TR was ligand-dependent and isoform-specific. Neither TR beta 1 nor TR beta 2 cotransfection inhibited estrogen-induced CAT activity, although both TR alpha and TR beta can bind to a consensus ER response element. Furthermore, cotransfection of a mutated TR alpha 1 that lacks binding to the AGGTCA sequence also inhibited the estrogen effect. Thus, the repression of estrogen action by liganded TR alpha 1 may involve protein-protein interactions although competition of ER and TR at the DNA level cannot be excluded. A similar inhibitory effect of liganded TR alpha 1 on estrogen induction of CAT activity was observed in a construct containing the preproenkephalin (PPE) promoter. A study in hypophysectomized female rats demonstrated that the estrogen-induced increase in PPE mRNA levels in the ventromedial hypothalamus was diminished by coadministration of triiodothyronine. These results suggest that ER and TR may interact to modulate estrogen-sensitive gene expression, such as for PPE, in the hypothalamus.

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Crossref · 10.1073/pnas.93.22.12587

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Authors
Zhu, Y. S., Yen, P. M., Chin, W. W., & Pfaff, D. W.
Affiliations
  • Rockefeller University (US)
  • Brigham and Women's Hospital (US)
Venue
Proceedings of the National Academy of Sciences
Published
1996-10-29
Volume
93
Issue
22
Pages
12587-12592
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2048959229
Cited by
143
References
42
Citations by year
2026: 2 · 2025: 1 · 2024: 3 · 2023: 2 · 2022: 2 · 2021: 2 · 2020: 1 · 2019: 1 · 2018: 2 · 2017: 2 · 2016: 2 · 2015: 3 · 2013: 2 · 2012: 4
FWCI
7.00
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK35500)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD05751)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
Keywords
estrogen receptor, thyroid hormone receptor, gene expression regulation, triiodothyronine, receptor isoforms, protein-protein interaction, hormone response elements, preproenkephalin, ventromedial hypothalamus, transcriptional repression
MeSH terms
Animals, Enkephalins, Estrogens, Female, Gene Expression Regulation, Hypophysectomy, Hypothalamus, Promoter Regions, Genetic, Protein Precursors, Receptors, Estrogen, Receptors, Thyroid Hormone, RNA, Messenger, Thymidine Kinase, Transcription, Genetic, Triiodothyronine, Chloramphenicol O-Acetyltransferase, Genes, Reporter, Rats

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