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Titolo:
Alteration in sexually dimorphic testosterone biotransformation profiles as a biomarker of chemically induced androgen disruption in mice
Autore:
Wilson, VS; McLachlan, JB; Falls, JG; LeBlanc, GA;
Indirizzi:
N Carolina State Univ, Dept Toxicol, Raleigh, NC 27695 USA N Carolina State Univ Raleigh NC USA 27695 Toxicol, Raleigh, NC 27695 USA
Titolo Testata:
ENVIRONMENTAL HEALTH PERSPECTIVES
fascicolo: 5, volume: 107, anno: 1999,
pagine: 377 - 384
SICI:
0091-6765(199905)107:5<377:AISDTB>2.0.ZU;2-Y
Fonte:
ISI
Lingua:
ENG
Soggetto:
ORAL-CONTRACEPTIVE STEROIDS; PLASMA TESTOSTERONE; ENVIRONMENTAL ESTROGENS; CONGENITAL-MALFORMATIONS; HYDROXYLASE-ACTIVITIES; HORMONAL-REGULATION; EXTERNAL GENITALIA; LIVER-MICROSOMES; BREAST-CANCER; SEX STEROIDS;
Keywords:
androgen disruption; biomarker; biotransformation; sexually dimorphic metabolism; testosterone;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Agriculture,Biology & Environmental Sciences
Life Sciences
Citazioni:
87
Recensione:
Indirizzi per estratti:
Indirizzo: LeBlanc, GA N Carolina State Univ, Dept Toxicol, Box 7633, Raleigh, NC 27695 USA N Carolina State Univ Box 7633 Raleigh NC USA 27695 27695 USA
Citazione:
V.S. Wilson et al., "Alteration in sexually dimorphic testosterone biotransformation profiles as a biomarker of chemically induced androgen disruption in mice", ENVIR H PER, 107(5), 1999, pp. 377-384

Abstract

Assessment of the impact of environmental chemicals on androgen homeostasis in rodent models is confounded by high intraindividual and interindividual variability in circulating testosterone levels. Our goal was to evaluate changes in testosterone biotransformation processes as a measure of androgen homeostasis and as a biomarker of exposure to androgen-disrupting chemicals. Sex-specific differences in hepatic testosterone biotransformation enzyme activities were identified in CD-1 mice. Gonadectomy followed by replacement of individual steroid hormones identified specific sex differences in biotransformation profiles that were due to the inductive or suppressive effects of testosterone. Notably, significant androgen-dependent differences in testosterone 6 alpha- and 15 alpha-hydroxylase activities were demonstrated, and the ratio of 6 alpha- and 15 alpha-hydroxylase activities proved to be an excellent indicator of the androgen status within the animal. The male or "masculinized" testosterone 6 alpha/15 alpha-hydroxylase ratio was significantly less than the female or "feminized" ratio. Male mice were exposed to both an antiandrogen, vinclozolin, and to a compound that modulates serum androgen levels, indole-3-carbinol, to test the utility of this ratioas a biomarker of androgen disruption. Treatment with the antiandrogen vinclozolin significantly increased the 6 alpha/15 alpha-hydroxylase ratio. Indole-3-carbinol treatment resulted in a dose-dependent, but highly variable, decrease in serum testosterone levels. The 6 alpha/15 alpha-hydroxylase ratio increased as serum testosterone levels decreased in these animals. However, the increase in the ratio was much less variable and more sensitive than serum testosterone levels. These investigations demonstrate that the 6 alpha/15 alpha-hydroxylase ratio is a powerful measure of androgen modulation and a sensitive indicator of exposure to androgen-disrupting chemicals in CD-1 mice.

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Documento generato il 05/07/20 alle ore 03:05:21