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Titolo:
7,12-dimethylbenz[a]anthracene inhibition of steroid production in MA-10 mouse leydig tumor cells is not directly linked to induction of CYP1B1
Autore:
Mandal, PK; McDaniel, LR; Prough, RA; Clark, BJ;
Indirizzi:
Univ Louisville, Sch Med, Dept Biochem & Mol Biol, Louisville, KY 40292 USA Univ Louisville Louisville KY USA 40292 ol Biol, Louisville, KY 40292 USA Louisville Vet Adm Ctr, Vet Adm Ctr Study Environm Hazards Reprod Hlth, Louisville, KY 40206 USA Louisville Vet Adm Ctr Louisville KY USA 40206 , Louisville, KY 40206 USA
Titolo Testata:
TOXICOLOGY AND APPLIED PHARMACOLOGY
fascicolo: 3, volume: 175, anno: 2001,
pagine: 200 - 208
SICI:
0041-008X(20010915)175:3<200:7IOSPI>2.0.ZU;2-D
Fonte:
ISI
Lingua:
ENG
Soggetto:
ACUTE REGULATORY PROTEIN; AROMATIC HYDROCARBON METABOLISM; ISOLATED ADRENAL-CELLS; 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN-TREATED RATS; ADULT-RATS; IN-VITRO; CYTOCHROME-P450; STEROIDOGENESIS; CHOLESTEROL; EXPRESSION;
Keywords:
TCDD; DMBA; steroidogenesis; CYP1B1; leydig cell;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
42
Recensione:
Indirizzi per estratti:
Indirizzo: Clark, BJ Univ Louisville, Sch Med, Dept Biochem & Mol Biol, Louisville, KY 40292 USA Univ Louisville Louisville KY USA 40292 ouisville, KY 40292 USA
Citazione:
P.K. Mandal et al., "7,12-dimethylbenz[a]anthracene inhibition of steroid production in MA-10 mouse leydig tumor cells is not directly linked to induction of CYP1B1", TOX APPL PH, 175(3), 2001, pp. 200-208

Abstract

Testosterone, which is essential for spermatogenesis, is synthesized in the Leydig cells of the testis. This study addresses whether male reproductive toxicity from exposure to polycyclic or polychlorinated aromatic hydrocarbons, such as 7,12-dimethylbenz[a]anthracene (DMBA) or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), may be due to direct effects on Leydig cell function. Using a cell-based assay, the effects of TCDD, benz[a]anthracene (BA), and DMBA on steroid production and cytochrome P4501B1 (CYP1B1) expression intreated MA-10 mouse Leydig tumor cells or primary cultures of rat Leydig cells was determined. (BU)(2)cAMP-stimulated steroid production was inhibited similar to 25% and similar to 80% by DMBA treatment of MA-10 cells and rat Leydig cells, respectively, while BA or TCDD were without effect. Conversely, male Sprague-Dawley rats treated with TCDD displayed a 75% decrease inserum testosterone levels, while DMBA-treated rats had circulating testosterone levels comparable to control rats. Injection of human chorionic gonadotropin (hCG) I h prior to euthanasia restored testosterone levels in TCDD-treated rats to 79% of the hCG-stimulated levels in control rats. Steady-state levels of CYP1B1 mRNA, as detected by RT-PCR, are present in the MA-10 cells and treatment with TCDD, BA, DMBA, or the cAMP analog (BU)(2)cAMP induced CYP1B1 mRNA expression levels. CYP1B1 was constitutively expressed in rat testis, adrenal, liver, and kidney tissues while CYP1A1 was undetectable. TCDD treatment induced CYP1B1 expression in the adrenal and liver and CYP1A1 in the kidney and liver. DMBA treatment induced only CYP1A1 levels in kidney and liver. In sum, DMBA or a reactive DMBA metabolite, but not TCDD,has a direct effect on steroidogenesis in isolated Leydig cells. CYP1B1 expression levels, however, cannot be directly correlated to potential in vitro or in vivo toxic effects of TCDD or DMBA. (C) 2001 Academic Press.

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Documento generato il 28/11/20 alle ore 15:25:51