The DOI matches its Crossref record; 71 of the 71 references it cites were found in a registry or an index.
Glucocorticoid Receptor Binding to a Specific DNA Sequence Is Required for Hormone-Dependent Repression of Pro-Opiomelanocortin Gene Transcription
Open accessAbstract
Glucocorticoids rapidly and specifically inhibit transcription of the pro-opiomelanocortin (POMC) gene in the anterior pituitary, thus offering a model for studying negative control of transcription in mammals. We have defined an element within the rat POMC gene 5'-flanking region that is required for glucocorticoid inhibition of POMC gene transcription in POMC-expressing pituitary tumor cells (AtT-20). This element contains an in vitro binding site for purified glucocorticoid receptor. Site-directed mutagenesis revealed that binding of the receptor to this site located at position base pair -63 is essential for glucocorticoid repression of transcription. Although related to the well-defined glucocorticoid response element (GRE) found in glucocorticoid-inducible genes, the DNA sequence of the POMC negative glucocorticoid response element (nGRE) differs significantly from the GRE consensus; this sequence divergence may result in different receptor-DNA interactions and may account at least in part for the opposite transcriptional properties of these elements. Hormone-dependent repression of POMC gene transcription may be due to binding of the receptor over a positive regulatory element of the promoter. Thus, repression may result from mutually exclusive binding of two DNA-binding proteins to overlapping DNA sequences.
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“Inhibition of CRH and ACTH induced by exogenous glucocorticoids is similar to the mechanisms involved in the physiologic cortisol negative feedback (16).”
From European Society of Endocrinology and Endocrine Society Joint Clinical Guideline: Diagnosis and Therapy of Glucocorticoid-induced Adrenal Insufficiency (2024) · cites this paper as [16]
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Nuclear Hormone Receptors and Gene Expression
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Metadata
- Authors
- Drouin, J., Trifiro, M. A., Plante, R. K., Nemer, M., Eriksson, P., & Wrange, Ö.
- Affiliations
- Montreal Clinical Research Institute (CA)
- Karolinska Institutet (SE)
- Department of Molecular Genetics, Karolinska Institutet
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 1989-12
- Volume
- 9
- Issue
- 12
- Pages
- 5305-5314
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC363695
- OpenAlex
- W2161628453
- Cited by
- 283
- References
- 71
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 3 · 2022: 5 · 2021: 5 · 2020: 4 · 2019: 4 · 2018: 5 · 2017: 2 · 2016: 5 · 2015: 3 · 2014: 2 · 2013: 6 · 2012: 2
- FWCI
- 12.99
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Biology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- glucocorticoid receptor, transcriptional repression, glucocorticoid response element, anterior pituitary, AtT-20 cells, sequence divergence
- MeSH terms
- Animals, Base Sequence, DNA, Genes, Molecular Sequence Data, Nucleotide Mapping, Pituitary Gland, Anterior, Plasmids, Pro-Opiomelanocortin, Protein Binding, Receptors, Glucocorticoid, Suppression, Genetic, Transcription, Genetic, Restriction Mapping, Rats
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