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Article: Modulation of steroidogenic gene expression and hormone production of H295R cells by pharmaceuticals and other environmentally active compounds

TitleModulation of steroidogenic gene expression and hormone production of H295R cells by pharmaceuticals and other environmentally active compounds
Authors
Issue Date2007
PublisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/taap
Citation
Toxicology And Applied Pharmacology, 2007, v. 225 n. 2, p. 142-153 How to Cite?
AbstractThe H295R cell bioassay was used to evaluate the potential endocrine disrupting effects of 18 of the most commonly used pharmaceuticals in the United States. Exposures for 48 h with single pharmaceuticals and binary mixtures were conducted; the expression of five steroidogenic genes, 3βHSD2, CYP11β1, CYP11β2, CYP17 and CYP19, was quantified by Q-RT-PCR. Production of the steroid hormones estradiol (E2), testosterone (T) and progesterone (P) was also evaluated. Antibiotics were shown to modulate gene expression and hormone production. Amoxicillin up-regulated the expression of CYP11β2 and CYP19 by more than 2-fold and induced estradiol production up to almost 3-fold. Erythromycin significantly increased CYP11β2 expression and the production of P and E2 by 3.5- and 2.4-fold, respectively, while production of T was significantly decreased. The β-blocker salbutamol caused the greatest induction of CYP17, more than 13-fold, and significantly decreased E2 production. The binary mixture of cyproterone and salbutamol significantly down-regulated expression of CYP19, while a mixture of ethynylestradiol and trenbolone, increased E2 production 3.7-fold. Estradiol production was significantly affected by changes in concentrations of trenbolone, cyproterone, and ethynylestradiol. Exposures with individual pharmaceuticals showed the possible secondary effects that drugs may exert on steroid production. Results from binary mixture exposures suggested the possible type of interactions that may occur between drugs and the joint effects product of such interactions. Dose-response results indicated that although two chemicals may share a common mechanism of action the concentration effects observed may be significantly different. © 2007 Elsevier Inc. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/179021
ISSN
2015 Impact Factor: 3.847
2015 SCImago Journal Rankings: 1.593
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorGracia, Ten_US
dc.contributor.authorHilscherova, Ken_US
dc.contributor.authorJones, PDen_US
dc.contributor.authorNewsted, JLen_US
dc.contributor.authorHigley, EBen_US
dc.contributor.authorZhang, Xen_US
dc.contributor.authorHecker, Men_US
dc.contributor.authorMurphy, MBen_US
dc.contributor.authorYu, RMKen_US
dc.contributor.authorLam, PKSen_US
dc.contributor.authorWu, RSSen_US
dc.contributor.authorGiesy, JPen_US
dc.date.accessioned2012-12-19T09:51:29Z-
dc.date.available2012-12-19T09:51:29Z-
dc.date.issued2007en_US
dc.identifier.citationToxicology And Applied Pharmacology, 2007, v. 225 n. 2, p. 142-153en_US
dc.identifier.issn0041-008Xen_US
dc.identifier.urihttp://hdl.handle.net/10722/179021-
dc.description.abstractThe H295R cell bioassay was used to evaluate the potential endocrine disrupting effects of 18 of the most commonly used pharmaceuticals in the United States. Exposures for 48 h with single pharmaceuticals and binary mixtures were conducted; the expression of five steroidogenic genes, 3βHSD2, CYP11β1, CYP11β2, CYP17 and CYP19, was quantified by Q-RT-PCR. Production of the steroid hormones estradiol (E2), testosterone (T) and progesterone (P) was also evaluated. Antibiotics were shown to modulate gene expression and hormone production. Amoxicillin up-regulated the expression of CYP11β2 and CYP19 by more than 2-fold and induced estradiol production up to almost 3-fold. Erythromycin significantly increased CYP11β2 expression and the production of P and E2 by 3.5- and 2.4-fold, respectively, while production of T was significantly decreased. The β-blocker salbutamol caused the greatest induction of CYP17, more than 13-fold, and significantly decreased E2 production. The binary mixture of cyproterone and salbutamol significantly down-regulated expression of CYP19, while a mixture of ethynylestradiol and trenbolone, increased E2 production 3.7-fold. Estradiol production was significantly affected by changes in concentrations of trenbolone, cyproterone, and ethynylestradiol. Exposures with individual pharmaceuticals showed the possible secondary effects that drugs may exert on steroid production. Results from binary mixture exposures suggested the possible type of interactions that may occur between drugs and the joint effects product of such interactions. Dose-response results indicated that although two chemicals may share a common mechanism of action the concentration effects observed may be significantly different. © 2007 Elsevier Inc. All rights reserved.en_US
dc.languageengen_US
dc.publisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/taapen_US
dc.relation.ispartofToxicology and Applied Pharmacologyen_US
dc.subject.mesh3-Hydroxysteroid Dehydrogenases - Drug Effects - Geneticsen_US
dc.subject.meshAdrenocortical Carcinoma - Metabolismen_US
dc.subject.meshAldosterone Synthase - Drug Effects - Geneticsen_US
dc.subject.meshAromatase - Drug Effects - Geneticsen_US
dc.subject.meshCell Line, Tumoren_US
dc.subject.meshCytochrome P-450 Enzyme System - Drug Effects - Geneticsen_US
dc.subject.meshDose-Response Relationship, Drugen_US
dc.subject.meshDrug Interactionsen_US
dc.subject.meshEndocrine Disruptors - Pharmacologyen_US
dc.subject.meshEstradiol - Biosynthesisen_US
dc.subject.meshGene Expression Regulation - Drug Effectsen_US
dc.subject.meshGonadal Steroid Hormones - Biosynthesisen_US
dc.subject.meshHumansen_US
dc.subject.meshProgesterone - Biosynthesisen_US
dc.subject.meshReverse Transcriptase Polymerase Chain Reactionen_US
dc.subject.meshSteroid 11-Beta-Hydroxylase - Drug Effects - Geneticsen_US
dc.subject.meshSteroid 17-Alpha-Hydroxylase - Drug Effects - Geneticsen_US
dc.subject.meshTestosterone - Biosynthesisen_US
dc.titleModulation of steroidogenic gene expression and hormone production of H295R cells by pharmaceuticals and other environmentally active compoundsen_US
dc.typeArticleen_US
dc.identifier.emailWu, RSS: rudolfwu@hku.hken_US
dc.identifier.authorityWu, RSS=rp01398en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1016/j.taap.2007.07.013en_US
dc.identifier.pmid17822730-
dc.identifier.scopuseid_2-s2.0-36048929219en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-36048929219&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume225en_US
dc.identifier.issue2en_US
dc.identifier.spage142en_US
dc.identifier.epage153en_US
dc.identifier.isiWOS:000251332200003-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridGracia, T=6506058618en_US
dc.identifier.scopusauthoridHilscherova, K=6603438103en_US
dc.identifier.scopusauthoridJones, PD=34771015600en_US
dc.identifier.scopusauthoridNewsted, JL=6603677236en_US
dc.identifier.scopusauthoridHigley, EB=13004073100en_US
dc.identifier.scopusauthoridZhang, X=8606600100en_US
dc.identifier.scopusauthoridHecker, M=35247848500en_US
dc.identifier.scopusauthoridMurphy, MB=7403900446en_US
dc.identifier.scopusauthoridYu, RMK=9278574900en_US
dc.identifier.scopusauthoridLam, PKS=7202365776en_US
dc.identifier.scopusauthoridWu, RSS=7402945079en_US
dc.identifier.scopusauthoridGiesy, JP=35459135300en_US

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