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Effects of brominated flame retardants and brominated dioxins on steroidogenesis in H295R human adrenocortical carcinoma cell line
Abstract
Brominated flame retardants (BFRs) and brominated dioxins are emerging persistent organic pollutants that are ubiquitous in the environment and can be accumulated by wildlife and humans. These chemicals can disturb endocrine function. Recent studies have demonstrated that one of the mechanisms of endocrine disruption by chemicals is modulation of steroidogenic gene expression or enzyme activities. In this study, an in vitro assay based on the H295R human adrenocortical carcinoma cell line, which possesses most key genes or enzymes involved in steroidogenesis, was used to examine the effects of five bromophenols, two polybrominated biphenyls (PBBs 77 and 169), 2,3,7,8-tetrabromodibenzo-p-dioxin, and 2,3,7,8-tetrabromodibenzofuran on the expression of 10 key steroidogenic genes. The H295R cells were exposed to various BFR concentrations for 48 h, and the expression of specific genes--cytochrome P450 (CYP11A, CYP11B2, CYP17, CYP19, and CYP21), beta-hydroxysteroid dehydrogenase (3betaHSD2), 17beta-hydroxysteroid dehydrogenase (17betaHSD1 and 17betaHSD4), steroidogenic acute regulatory protein (StAR), and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR)--was quantitatively measured using real-time polymerase chain reaction. Cell viability was not affected at the doses tested. Most of the genes were either up- or down-regulated, to some extent, by BFR exposure. Among the genes tested, 3betaHSD2 was the most markedly up-regulated, with a range of magnitude from 1.6- to 20-fold. The results demonstrate that bromophenol, bromobiphenyls, and bromodibenzo-p-dioxin/furan are able to modulate steroidogenic gene expression, which may lead to endocrine disruption.
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CYP21A1P transcripts cannot be detected in primary cultures of human adrenocortical cells, whereas CYP21A2 is appropriately expressed under the same conditions.
“Similarly, CYP21A1P transcripts cannot be detected in primary cultures of human adrenocortical cells, whereas CYP21A2 is appropriately expressed under the same conditions (170,176).”
From Congenital Adrenal Hyperplasia—Current Insights in Pathophysiology, Diagnostics, and Management (2022) · cites this paper as [170]
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Congenital Adrenal Hyperplasia—Current Insights in Pathophysiology, Diagnostics, and Management
Claahsen - van der Grinten, H. L., Speiser, P. W., Ahmed, S. F., Arlt, W., Auchus, R. J., Falhammar, H., Flück, C. E., Guasti, L., Huebner, A., Kortmann, B. B. M., et al. (2022) · Endocrine Reviews · doi:10.1210/endrev/bnab016 · Cited by 556
Metadata
- Authors
- Ding, L., Murphy, M. B., He, Y., Xu, Y., Yeung, L. W. Y., Wang, J., Zhou, B., Lam, P. K. S., Wu, R. S. S., & Giesy, J. P.
- Affiliations
- Chinese Academy of Sciences (CN)
- City University of Hong Kong (HK)
- Michigan State University (US)
- Corresponding author
- Zhou, Bingsheng
- ORCID
- Venue
- Environmental Toxicology and Chemistry
- Publisher
- Oxford University Press (OUP)
- Published
- 2007-04-01
- Volume
- 26
- Issue
- 4
- Pages
- 764-772
- ISSN
- 0730-7268 (ISSN-L)
- 1552-8618
- OpenAlex
- W2095406777
- Cited by
- 51
- References
- 41
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 2 · 2022: 3 · 2021: 1 · 2020: 3 · 2019: 2 · 2018: 2 · 2017: 2 · 2016: 5 · 2015: 5 · 2014: 2 · 2013: 3 · 2012: 1
- FWCI
- 2.78
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Environmental Toxicology and Chemistry (publishedVersion)
- PubMed (publishedVersion)
- The HKU Scholars Hub (University of Hong Kong) (submittedVersion)
- Institute of Hydrobiology, CAS Institutional Repository (submittedVersion)
- Topics
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
- Physical Sciences › Environmental Science › Environmental Chemistry › Per- and polyfluoroalkyl substances research
- Keywords
- brominated flame retardants, brominated dioxins, bromophenols, polybrominated biphenyls, steroidogenesis, endocrine disruption, steroidogenic gene expression, H295R cells, 3β-hydroxysteroid dehydrogenase, cytochrome P450, stars, HMGR, persistent organic pollutants
- MeSH terms
- Steroidogenic Acute Regulatory Protein, Cell Survival, Cytochrome P-450 Enzyme System, Dioxins, Dose-Response Relationship, Drug, Flame Retardants, Gene Expression Regulation, Humans, Hydrocarbons, Brominated, Hydroxymethylglutaryl CoA Reductases, Phosphoproteins, Steroids, 17-Hydroxysteroid Dehydrogenases, 3-Hydroxysteroid Dehydrogenases, Polymerase Chain Reaction, DNA Primers, DNA, Complementary, Cell Line, Tumor
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