Estrogen and thyroid hormone interaction on regulation of gene expression.
Open accessAbstract
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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- 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
- Publisher
- National Academy of Sciences
- Published
- 1996-10-29
- Volume
- 93
- Issue
- 22
- Pages
- 12587-12592
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC38036
- 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
- green
- www.ncbi.nlm.nih.gov
- 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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