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Titolo:
Disruption of androgen-regulated male reproductive development by Di(n-butyl) phthalate during late gestation in rats is different from flutamide
Autore:
Mylchreest, E; Sar, M; Cattley, RC; Foster, PMD;
Indirizzi:
Chem Ind Inst Toxicol, Res Triangle Pk, NC 27709 USA Chem Ind Inst Toxicol Res Triangle Pk NC USA 27709 angle Pk, NC 27709 USA
Titolo Testata:
TOXICOLOGY AND APPLIED PHARMACOLOGY
fascicolo: 2, volume: 156, anno: 1999,
pagine: 81 - 95
SICI:
0041-008X(19990415)156:2<81:DOAMRD>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
ANTIANDROGEN FLUTAMIDE; TESTICULAR DESCENT; UROGENITAL TRACT; EXPOSURE; RECEPTOR; 5-ALPHA-REDUCTASE; CRYPTORCHIDISM; INHIBITOR; ESTROGENS; ESTERS;
Keywords:
phthalate; di(n-butyl; flutamide; reproductive development; Leydig cell hyperplasia; androgen receptor;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
36
Recensione:
Indirizzi per estratti:
Indirizzo: Mylchreest, E Chem Ind Inst Toxicol, Res Triangle Pk, NC 27709 USA Chem Ind Inst Toxicol Res Triangle Pk NC USA 27709 7709 USA
Citazione:
E. Mylchreest et al., "Disruption of androgen-regulated male reproductive development by Di(n-butyl) phthalate during late gestation in rats is different from flutamide", TOX APPL PH, 156(2), 1999, pp. 81-95

Abstract

Gestational and lactational exposure to di(n-butyl) phthalate (DBP) at greater than or equal to 250 mg/kg/day disrupts male rat reproductive development and function. Although this indicates an antiandrogenic mechanism, DBP and its biologically active metabolite do not interact with the androgen receptor (AR) in vitro. In the present study, we compared the effects of DBP and the antiandrogen flutamide using a shorter exposure during the prenatalperiod of male sexual differentiation in rats. Pregnant CD rats received DBP at 0, 100, 250, or 500 mg/kg/day po (n = 10) or flutamide at 100 mg/kg/day po (n = 5) from Gestation Days 12 to 21. In F-1 males, DBP (500 mg/kg/day) and flutamide caused hypospadias; cryptorchidism; agenesis of the prostate, epididymis, and vas deferens; degeneration of the seminiferous epithelium; and interstitial cell hyperplasia of the testis. Flutamide and DBP (250and 500 mg/kg/day) also produced retained thoracic nipples and decreased anogenital distance. Interstitial cell adenoma occurred at 500 mg DBP/kg/dayin two males. The only effect seen at 100 mg DBP/kg/day was delayed preputial separation. In contrast to flutamide, DBP caused a low incidence of prostate agenesis and hypospadias with no vaginal pouch. The low incidence of DBP-induced intraabdominal testes contrasted with the high incidence of inguinal testes seen with flutamide. Thus prenatal male sexual differentiationis a sensitive period for the reproductive toxicity of DBP. A no observed adverse effect level was not established and the lowest observed (adverse) effect level was 100 mg/kg/day. Flutamide and DBP disrupted the androgen signaling necessary for male sexual differentiation but with a different pattern of antiandrogenic effects. DBP is an example of an environmental antiandrogen that disrupts androgen-regulated male sexual differentiation withoutinteracting directly With the AR, as does flutamide. (C) 1999 Academic Press.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 26/11/20 alle ore 11:47:02