Evidence of direct estrogenic regulation of human corticotropin-releasing hormone gene expression. Potential implications for the sexual dimophism of the stress response and immune/inflammatory reaction.
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Corticotropin-releasing hormone (CRH) plays major roles in coordination of the stress response and regulation of the immune/inflammatory reaction, two important functions associated with sexual dimorphism. Two overlapping segments of the 5' flanking region of the human (h) CRH gene, the proximal 0.9 kb (containing two perfect half-palindromic estrogen-responsive elements [EREs]) and the 2.4 kb (including the former and containing two additional perfect half-palindromic EREs), were examined for their ability to confer estrogen-mediated transcriptional enhancement to a homologous or heterologous promoter. The level of estrogen-induced transactivation by the 0.9- and 2.4-kb segments was determined by chloramphenicol acetyltransferase analysis in CV-1 cells cotransfected with estrogen receptor (ER) cDNA expression plasmids, and found to be respectively approximately 10% and 20% of that of the strongly estrogen-responsive Xenopus vitellogenin A2 enhancer. Gel retardation and immunoprecipitation demonstrated specific association between the perfect half-palindromic EREs of hCRH gene and the DNA binding domain of hER in vitro. These findings may constitute the basis of sexual dimorphism in the expression of the CRH gene in the central nervous system and periphery, and might shed light in existing gender differences in stress response and immune regulation.
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Estradiol treatment increases human Crh promoter activity by almost twofold in vitro in cells co-transfected with ERα and a Crh promoter-reporter gene construct.
“In support of this, they showed that estradiol treatment increased human Crh promoter activity by almost twofold in vitro in cells co-transfected with the ER α and a Crh promoter–reporter gene construct.”
From Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity (2017) · cites this paper as Vamvakopoulos & Chrousos, 1993
The Crh promoter contains several ERE half sites.
“Examination of the regulation of CRH by estradiol was first described by Vamvakopoulos & Chrousos (1993), who demonstrated that the Crh promoter contains several ERE half sites, suggesting the involvement of ERE-mediated effects of estrogen receptor.”
From Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity (2017) · cites this paper as Vamvakopoulos & Chrousos, 1993
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- Authors
- Vamvakopoulos, N. C., & Chrousos, G. P.
- Affiliations
- National Institutes of Health (US)
- ORCID
- Chrousos, G P
- Venue
- Journal of Clinical Investigation
- Published
- 1993-10-01
- Volume
- 92
- Issue
- 4
- Pages
- 1896-1902
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC288355
- OpenAlex
- W2024837798
- Cited by
- 422
- References
- 61
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 3 · 2023: 6 · 2022: 6 · 2021: 12 · 2020: 8 · 2019: 7 · 2018: 15 · 2017: 7 · 2016: 17 · 2015: 14 · 2014: 12 · 2013: 18 · 2012: 12
- FWCI
- 7.82
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- corticotropin-releasing factor, CRH gene expression, estrogen response element, estrogen receptor, 5'-flanking region, sexual dimorphism, stress response, immune regulation, inflammation, DNA-binding domain, gender differences
- MeSH terms
- Amino Acid Sequence, Animals, Base Sequence, Cell Line, Corticotropin-Releasing Hormone, Enhancer Elements, Genetic, Female, Gene Expression Regulation, Humans, Immunity, Male, Molecular Sequence Data, Oligodeoxyribonucleotides, Promoter Regions, Genetic, Protein Conformation, Receptors, Estrogen, Recombinant Proteins, Sex Characteristics, Stress, Physiological, Transcription, Genetic, Transfection, Vitellogenins, Xenopus, Restriction Mapping, Chloramphenicol O-Acetyltransferase, Zinc Fingers, TATA Box
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