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- Publisher Website: 10.1677/joe.1.06054
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- PMID: 15930178
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Article: Inhibition of CYP450scc expression in dioxin-exposed rat Leydig cells
Title | Inhibition of CYP450scc expression in dioxin-exposed rat Leydig cells |
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Authors | |
Issue Date | 2005 |
Publisher | Society 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? |
Abstract | Polychlorinated 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 Identifier | http://hdl.handle.net/10722/183393 |
ISSN | 2023 Impact Factor: 3.4 2023 SCImago Journal Rankings: 1.159 |
ISI Accession Number ID | |
References |
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Lai, KP | en_US |
dc.contributor.author | Wong, MH | en_US |
dc.contributor.author | Wong, CKC | en_US |
dc.date.accessioned | 2013-05-27T07:12:31Z | - |
dc.date.available | 2013-05-27T07:12:31Z | - |
dc.date.issued | 2005 | en_US |
dc.identifier.citation | Journal Of Endocrinology, 2005, v. 185 n. 3, p. 519-527 | en_US |
dc.identifier.issn | 0022-0795 | en_US |
dc.identifier.uri | http://hdl.handle.net/10722/183393 | - |
dc.description.abstract | Polychlorinated 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.language | eng | en_US |
dc.publisher | Society for Endocrinology. The Journal's web site is located at http://joe.endocrinology-journals.org | en_US |
dc.relation.ispartof | Journal of Endocrinology | en_US |
dc.subject.mesh | 3-Hydroxysteroid Dehydrogenases - Genetics - Metabolism | en_US |
dc.subject.mesh | Animals | en_US |
dc.subject.mesh | Blotting, Western - Methods | en_US |
dc.subject.mesh | Cell Culture Techniques | en_US |
dc.subject.mesh | Cholesterol Side-Chain Cleavage Enzyme - Metabolism | en_US |
dc.subject.mesh | Cyclic Amp - Metabolism | en_US |
dc.subject.mesh | Cytochrome P-450 Cyp1a1 - Genetics - Metabolism | en_US |
dc.subject.mesh | Depression, Chemical | en_US |
dc.subject.mesh | Leydig Cells - Drug Effects - Enzymology | en_US |
dc.subject.mesh | Male | en_US |
dc.subject.mesh | Progesterone - Genetics - Metabolism | en_US |
dc.subject.mesh | Rna, Messenger - Analysis | en_US |
dc.subject.mesh | Rats | en_US |
dc.subject.mesh | Rats, Sprague-Dawley | en_US |
dc.subject.mesh | Reverse Transcriptase Polymerase Chain Reaction | en_US |
dc.subject.mesh | Teratogens - Pharmacology | en_US |
dc.subject.mesh | Testosterone - Genetics - Metabolism | en_US |
dc.subject.mesh | Tetrachlorodibenzodioxin - Pharmacology | en_US |
dc.title | Inhibition of CYP450scc expression in dioxin-exposed rat Leydig cells | en_US |
dc.type | Article | en_US |
dc.identifier.email | Lai, KP: ballllai@hotmail.com | en_US |
dc.identifier.authority | Lai, KP=rp01753 | en_US |
dc.description.nature | link_to_subscribed_fulltext | en_US |
dc.identifier.doi | 10.1677/joe.1.06054 | en_US |
dc.identifier.pmid | 15930178 | - |
dc.identifier.scopus | eid_2-s2.0-21244443036 | en_US |
dc.relation.references | http://www.scopus.com/mlt/select.url?eid=2-s2.0-21244443036&selection=ref&src=s&origin=recordpage | en_US |
dc.identifier.volume | 185 | en_US |
dc.identifier.issue | 3 | en_US |
dc.identifier.spage | 519 | en_US |
dc.identifier.epage | 527 | en_US |
dc.identifier.isi | WOS:000229857800018 | - |
dc.publisher.place | United Kingdom | en_US |
dc.identifier.scopusauthorid | Lai, KP=7402135707 | en_US |
dc.identifier.scopusauthorid | Wong, MH=7403908633 | en_US |
dc.identifier.scopusauthorid | Wong, CKC=35276549400 | en_US |
dc.identifier.issnl | 0022-0795 | - |