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Article: Inhibition of CYP450scc expression in dioxin-exposed rat Leydig cells

TitleInhibition of CYP450scc expression in dioxin-exposed rat Leydig cells
Authors
Issue Date2005
PublisherSociety for Endocrinology. The Journal's web site is located at http://joe.endocrinology-journals.org
Citation
Journal Of Endocrinology, 2005, v. 185 n. 3, p. 519-527 How to Cite?
AbstractPolychlorinated dibenzo-p-dioxins, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) have been recognized as highly potent developmental and reproductive toxins. We have previously demonstrated effects of TCDD in modulating the expression of rat Sertoli cell secretory products and markers for cell-cell interaction. In this study, we examined the direct biological effects of TCDD in rat Leydig cell primary cultures. Mature rat Leydig cells were purified by Percoll gradient centrifugation and the cell purity was determined by 3β-hydroxysteroid dehydrogenase (3β-HSD) staining and a testosterone induction assay. To examine TCDD-induced biological consequences, we measured the changes in the secretion of progesterone and testosterone, as well as transcript levels of some selected steroidogenic enzymes (i.e. StAR, P450scc, 3β-HSD and CYP17α), in TCDD/human chorionic gonadotropin (hCG) co-treated cells. Our results indicated that TCDD (0.2 or 2 ng/ml) treatment significantly suppressed hCG (5 or 10 ng/ml)-induced testosterone secretion. The suppressive effect aligned with a reduction of progesterone secretion (P<0.05), as well as a decrease of P450scc mRNA and protein expression (P<0.05). The mechanistic action of TCDD was found to be via the reduction of cellular cAMP levels in the hCG-treated cells. This observation was further confirmed, as the TCDD-mediated suppressive effect could be reversed by dibutyryl cAMP co-treatment. The data indicate that TCDD can modulate cAMP signaling in rat Leydig cells to affect the process of steroidogenesis. © 2005 Society for Endocrinology.
Persistent Identifierhttp://hdl.handle.net/10722/183393
ISSN
2015 Impact Factor: 4.498
2015 SCImago Journal Rankings: 1.910
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLai, KPen_US
dc.contributor.authorWong, MHen_US
dc.contributor.authorWong, CKCen_US
dc.date.accessioned2013-05-27T07:12:31Z-
dc.date.available2013-05-27T07:12:31Z-
dc.date.issued2005en_US
dc.identifier.citationJournal Of Endocrinology, 2005, v. 185 n. 3, p. 519-527en_US
dc.identifier.issn0022-0795en_US
dc.identifier.urihttp://hdl.handle.net/10722/183393-
dc.description.abstractPolychlorinated dibenzo-p-dioxins, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) have been recognized as highly potent developmental and reproductive toxins. We have previously demonstrated effects of TCDD in modulating the expression of rat Sertoli cell secretory products and markers for cell-cell interaction. In this study, we examined the direct biological effects of TCDD in rat Leydig cell primary cultures. Mature rat Leydig cells were purified by Percoll gradient centrifugation and the cell purity was determined by 3β-hydroxysteroid dehydrogenase (3β-HSD) staining and a testosterone induction assay. To examine TCDD-induced biological consequences, we measured the changes in the secretion of progesterone and testosterone, as well as transcript levels of some selected steroidogenic enzymes (i.e. StAR, P450scc, 3β-HSD and CYP17α), in TCDD/human chorionic gonadotropin (hCG) co-treated cells. Our results indicated that TCDD (0.2 or 2 ng/ml) treatment significantly suppressed hCG (5 or 10 ng/ml)-induced testosterone secretion. The suppressive effect aligned with a reduction of progesterone secretion (P<0.05), as well as a decrease of P450scc mRNA and protein expression (P<0.05). The mechanistic action of TCDD was found to be via the reduction of cellular cAMP levels in the hCG-treated cells. This observation was further confirmed, as the TCDD-mediated suppressive effect could be reversed by dibutyryl cAMP co-treatment. The data indicate that TCDD can modulate cAMP signaling in rat Leydig cells to affect the process of steroidogenesis. © 2005 Society for Endocrinology.en_US
dc.languageengen_US
dc.publisherSociety for Endocrinology. The Journal's web site is located at http://joe.endocrinology-journals.orgen_US
dc.relation.ispartofJournal of Endocrinologyen_US
dc.subject.mesh3-Hydroxysteroid Dehydrogenases - Genetics - Metabolismen_US
dc.subject.meshAnimalsen_US
dc.subject.meshBlotting, Western - Methodsen_US
dc.subject.meshCell Culture Techniquesen_US
dc.subject.meshCholesterol Side-Chain Cleavage Enzyme - Metabolismen_US
dc.subject.meshCyclic Amp - Metabolismen_US
dc.subject.meshCytochrome P-450 Cyp1a1 - Genetics - Metabolismen_US
dc.subject.meshDepression, Chemicalen_US
dc.subject.meshLeydig Cells - Drug Effects - Enzymologyen_US
dc.subject.meshMaleen_US
dc.subject.meshProgesterone - Genetics - Metabolismen_US
dc.subject.meshRna, Messenger - Analysisen_US
dc.subject.meshRatsen_US
dc.subject.meshRats, Sprague-Dawleyen_US
dc.subject.meshReverse Transcriptase Polymerase Chain Reactionen_US
dc.subject.meshTeratogens - Pharmacologyen_US
dc.subject.meshTestosterone - Genetics - Metabolismen_US
dc.subject.meshTetrachlorodibenzodioxin - Pharmacologyen_US
dc.titleInhibition of CYP450scc expression in dioxin-exposed rat Leydig cellsen_US
dc.typeArticleen_US
dc.identifier.emailLai, KP: ballllai@hotmail.comen_US
dc.identifier.authorityLai, KP=rp01753en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1677/joe.1.06054en_US
dc.identifier.pmid15930178-
dc.identifier.scopuseid_2-s2.0-21244443036en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-21244443036&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume185en_US
dc.identifier.issue3en_US
dc.identifier.spage519en_US
dc.identifier.epage527en_US
dc.identifier.isiWOS:000229857800018-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridLai, KP=7402135707en_US
dc.identifier.scopusauthoridWong, MH=7403908633en_US
dc.identifier.scopusauthoridWong, CKC=35276549400en_US

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