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Article: Human adrenocarcinoma (H295R) cells for rapid in vitro determination of effects on steroidogenesis: Hormone production

TitleHuman adrenocarcinoma (H295R) cells for rapid in vitro determination of effects on steroidogenesis: Hormone production
Authors
KeywordsChemical screening
Endocrine disruption
Steroid hormones
Steroidogenesis
Issue Date2006
PublisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/taap
Citation
Toxicology And Applied Pharmacology, 2006, v. 217 n. 1, p. 114-124 How to Cite?
AbstractTo identify and prioritize chemicals that may alter steroidogenesis, an in vitro screening assay based on measuring alterations in hormone production was developed using the H295R human adrenocortical carcinoma cell line. Previous studies indicated that this cell line was useful to screen for effects on gene expression of steroidogenic enzymes. This study extended that work to measure the integrated response on production of testosterone (T), estradiol (E2), and progesterone/pregnenolone (P) using an ELISA. Under optimized culture and experimental conditions, the basal release of P, T and E2 into the medium was 7.0 ± 1.2 ng/ml, 1.6 ± 0.4 ng/ml, and 0.51 ± 0.13 ng/ml, respectively. Model chemicals with different modes of action on steroidogenic systems were tested. Exposure to forskolin resulted in dose-dependent increases in all three hormones with the greatest relative increase being observed for E2. This differed from cells exposed to prochloraz or ketoconazole where P concentrations increased while T and E2 concentrations decreased in a dose-dependent manner. In cells exposed to fadrozole, E2 decreased in a dose-dependent manner while T and P only decreased at the greatest dose tested. Aminoglutethimide decreased P and E2 concentrations but increased T concentrations. Vinclozolin reduced both P and T but resulted in a slight increase in E2. The alteration in the patterns of hormone production in the H295R assay was consistent with the modes of action of the chemicals and was also consistent with observed effects of these chemicals in animal models. Based on these results, the H295R in vitro system has potential for high throughput screening to not only characterize the effects of chemicals on endocrine systems but also to prioritize chemicals for additional testing. © 2006 Elsevier Inc. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/92778
ISSN
2015 Impact Factor: 3.847
2015 SCImago Journal Rankings: 1.593
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorHecker, Men_HK
dc.contributor.authorNewsted, JLen_HK
dc.contributor.authorMurphy, MBen_HK
dc.contributor.authorHigley, EBen_HK
dc.contributor.authorJones, PDen_HK
dc.contributor.authorWu, Ren_HK
dc.contributor.authorGiesy, JPen_HK
dc.date.accessioned2010-09-17T10:56:53Z-
dc.date.available2010-09-17T10:56:53Z-
dc.date.issued2006en_HK
dc.identifier.citationToxicology And Applied Pharmacology, 2006, v. 217 n. 1, p. 114-124en_HK
dc.identifier.issn0041-008Xen_HK
dc.identifier.urihttp://hdl.handle.net/10722/92778-
dc.description.abstractTo identify and prioritize chemicals that may alter steroidogenesis, an in vitro screening assay based on measuring alterations in hormone production was developed using the H295R human adrenocortical carcinoma cell line. Previous studies indicated that this cell line was useful to screen for effects on gene expression of steroidogenic enzymes. This study extended that work to measure the integrated response on production of testosterone (T), estradiol (E2), and progesterone/pregnenolone (P) using an ELISA. Under optimized culture and experimental conditions, the basal release of P, T and E2 into the medium was 7.0 ± 1.2 ng/ml, 1.6 ± 0.4 ng/ml, and 0.51 ± 0.13 ng/ml, respectively. Model chemicals with different modes of action on steroidogenic systems were tested. Exposure to forskolin resulted in dose-dependent increases in all three hormones with the greatest relative increase being observed for E2. This differed from cells exposed to prochloraz or ketoconazole where P concentrations increased while T and E2 concentrations decreased in a dose-dependent manner. In cells exposed to fadrozole, E2 decreased in a dose-dependent manner while T and P only decreased at the greatest dose tested. Aminoglutethimide decreased P and E2 concentrations but increased T concentrations. Vinclozolin reduced both P and T but resulted in a slight increase in E2. The alteration in the patterns of hormone production in the H295R assay was consistent with the modes of action of the chemicals and was also consistent with observed effects of these chemicals in animal models. Based on these results, the H295R in vitro system has potential for high throughput screening to not only characterize the effects of chemicals on endocrine systems but also to prioritize chemicals for additional testing. © 2006 Elsevier Inc. All rights reserved.en_HK
dc.languageengen_HK
dc.publisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/taapen_HK
dc.relation.ispartofToxicology and Applied Pharmacologyen_HK
dc.subjectChemical screeningen_HK
dc.subjectEndocrine disruptionen_HK
dc.subjectSteroid hormonesen_HK
dc.subjectSteroidogenesisen_HK
dc.titleHuman adrenocarcinoma (H295R) cells for rapid in vitro determination of effects on steroidogenesis: Hormone productionen_HK
dc.typeArticleen_HK
dc.identifier.emailWu, R: rudolfwu@hku.hken_HK
dc.identifier.authorityWu, R=rp01398en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.taap.2006.07.007en_HK
dc.identifier.pmid16962624-
dc.identifier.scopuseid_2-s2.0-33750351770en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-33750351770&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume217en_HK
dc.identifier.issue1en_HK
dc.identifier.spage114en_HK
dc.identifier.epage124en_HK
dc.identifier.eissn1096-0333-
dc.identifier.isiWOS:000241937100013-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridHecker, M=35247848500en_HK
dc.identifier.scopusauthoridNewsted, JL=6603677236en_HK
dc.identifier.scopusauthoridMurphy, MB=7403900446en_HK
dc.identifier.scopusauthoridHigley, EB=13004073100en_HK
dc.identifier.scopusauthoridJones, PD=34771015600en_HK
dc.identifier.scopusauthoridWu, R=7402945079en_HK
dc.identifier.scopusauthoridGiesy, JP=35459135300en_HK

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