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Titolo:
EXPRESSION OF CYTOCHROME-P450 17-ALPHA-HYDROXYLASE C17-20 LYASE IN THE FETAL-RAT TESTIS IS REDUCED BY MATERNAL EXPOSURE TO EXOGENOUS ESTROGENS/
Autore:
MAJDIC G; SHARPE RM; OSHAUGHNESSY PJ; SAUNDERS PTK;
Indirizzi:
MRC,REPROD BIOL UNIT,37 CHALMERS ST EDINBURGH EH3 9EW MIDLOTHIAN SCOTLAND MRC,REPROD BIOL UNIT EDINBURGH EH3 9EW MIDLOTHIAN SCOTLAND UNIV GLASGOW,DEPT VET PHYSIOL GLASGOW G61 1QH LANARK SCOTLAND
Titolo Testata:
Endocrinology
fascicolo: 3, volume: 137, anno: 1996,
pagine: 1063 - 1070
SICI:
0013-7227(1996)137:3<1063:EOC1CL>2.0.ZU;2-K
Fonte:
ISI
Lingua:
ENG
Soggetto:
STEROIDOGENIC ENZYME-ACTIVITY; LUTEINIZING-HORMONE; REPRODUCTIVE TRACTS; MOUSE TESTIS; LEYDIG-CELLS; MALE-MICE; RECEPTORS; DIETHYLSTILBESTROL; ESTRADIOL; TESTOSTERONE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
52
Recensione:
Indirizzi per estratti:
Citazione:
G. Majdic et al., "EXPRESSION OF CYTOCHROME-P450 17-ALPHA-HYDROXYLASE C17-20 LYASE IN THE FETAL-RAT TESTIS IS REDUCED BY MATERNAL EXPOSURE TO EXOGENOUS ESTROGENS/", Endocrinology, 137(3), 1996, pp. 1063-1070

Abstract

Testosterone is required for normal development of the male reproductive tract. Synthesis of testosterone occurs in the Leydig cells and isdependent upon the expression of several enzymes, including cytochrome P450 17 alpha-hydroxylase/C17-20-lyase (P450c17), which is highly regulated within the testis. The aim of the present study was to investigate whether maternal exposure to estrogenic chemicals was able to affect Leydig cell function in the developing male fetus at the time of masculinization. Pregnant rats were injected sc with diethylstilbestrol(DES; 100 or 500 mu g/kg), 4-octylphenol (OF; 100 or 609 mg/kg), or vehicle (oil, control) on days 11.5 and 15.5 postcoitum. Doses were chosen to reflect the reported estrogenic potency of the chemicals in vitro. On day 17.5, fetal testes were fixed before performing in situ hybridization and immunocytochemistry, used for extraction of RNA, or homogenized in phosphate buffer for determination of 17 alpha-hydroxylaseenzyme activity. There was no difference between fetuses from controland treated mothers in either the overall histology of the testes or the apparent number of Leydig cells, as determined by immunocytochemistry with an antibody directed against SP-hydroxysteroid dehydrogenase. However, there was a consistent and striking reduction in the amount of P450c17 detected by immunocytochemistry in testes from the groups given the higher dose of DES or OP. These observations were supported by measurement of 17 alpha-hydroxylase activity, which was significantly reduced compared with that in controls (6.25 +/- 0.65 pmol/testis . min) in fetuses from animals treated with 100 mu g/kg DES (4.27 +/- 0.39; P < 0.05), 500 mu g/kg DES (1.4 +/- 0.47; P < 0.001), or 600 mg/kgOP(4.25 +/- 0.33; P < 0.05). RT-PCR and in situ hybridization revealed that these changes were mirrored by reductions in P450c17 messenger RNA in testes from fetuses from treated mothers compared with control levels. In conclusion, maternal treatment with either a potent synthetic estrogen (DES) or a putative environmental estrogen (OF) results inreduced expression of the messenger RNA and protein for P450c17 in fetal Leydig cells. These results, therefore, provide a mechanism by which inappropriate exposure of the fetus to estrogenic chemicals might have an adverse affect on fetal steroid synthesis and masculinization.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 15/07/20 alle ore 07:24:35