Vinclozolin modulates hepatic cytochrome P450 isoforms during pregnancy.
Vinclozolin (V) is classified as a potent endocrine disruptor. The aim of the present study was to determine the effects of V on rat liver CYP regulation and on serum levels of testosterone and estradiol during pregnancy. Pregnancy decreased the liver total CYP content by 65%, enzyme activities of MROD, PROD, and PNPH, and testosterone hydroxylation activities, as well as the protein content of CYP2A and 3A. V exposure remarkably induced the protein content and enzyme activities of CYP1A, 2A, 2B and 3A subfamilies. Testosterone and estradiol were affected in an opposite manner, provoking a 3.5-fold increase in the estradiol/testosterone ratio. These results suggest that V could regulate the hepatic CYP expression through interaction with receptors and coactivators involved in its expression and may play an important role in hormonal balance during pregnancy. In addition, the results may also contribute to understanding the toxicity of V by in utero exposure.
Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (Cinvestav), Av. IPN No. 2508, Col. San Pedro Zacatenco, México, D.F. CP 07360, Mexico.
Félix Genoveva García-Montes
FG
de Oca
Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (Cinvestav), Av. IPN No. 2508, Col. San Pedro Zacatenco, México, D.F. CP 07360, Mexico.
Ma de Lourdes
Mde L
López-González
Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (Cinvestav), Av. IPN No. 2508, Col. San Pedro Zacatenco, México, D.F. CP 07360, Mexico.
Derly Constanza
DC
Escobar-Wilches
Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", Vasco de Quiroga No. 15, Col. Sección XVI, México, D.F. CP 14000, Mexico.
Roberto
R
Chavira-Ramírez
Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (Cinvestav), Av. IPN No. 2508, Col. San Pedro Zacatenco, México, D.F. CP 07360, Mexico. Electronic address: asierra@cinvestav.mx.
Adolfo
A
Sierra-Santoyo
D000726:Androgen Antagonists / Q000494:pharmacology*; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004958:Estradiol / Q000097:blood; D005260:Female; D007527:Isoenzymes / Q000096:biosynthesis; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D010080:Oxazoles / Q000494:pharmacology*; D011247:Pregnancy / Q000378:metabolism; D017208:Rats, Wistar; D013739:Testosterone / Q000097:blood
D000726:Androgen Antagonists; D007527:Isoenzymes; D010080:Oxazoles; D013739:Testosterone; D004958:Estradiol; D003577:Cytochrome P-450 Enzyme System; C025643:vinclozolin
Cytochrome P450; Endocrine disruption; Estradiol; Pregnancy; Testosterone; Vinclozolin