Abstract

The testicular steroids androstenone (A), 17 beta-oestradiol (E2) and testosterone (T) were tested for their ability to alter CYP2E1 and CYP2A activity in porcine liver microsomes from male and female pigs. This is the first in vitro study indicating that sex steroids have a potential to modify microsomal CYP2E1 activity, the main skatole-metabolising enzyme. A and E2 exerted an inhibitory effect on CYP2E1 mediated hydroxylation of p-nitrophenol to p-nitrocatechol although the mechanism of this inhibition differed for these steroids. The inhibitory effect of A on CYP2E1, as determined by kinetic analysis, might be due to the competitive binding of A and p-nitrophenol to the same site of CYP2E1. Including E2 into the incubations resulted in decreased activities of CYP2E1 in male microsomes through a mixed mode of inhibition. Including pre-incubation steps eliminated this inhibition in male microsomes, and resulted in increased CYP2E1 activities in the microsomes from female pigs. Testosterone was ineffective as an inhibitor of either CYP2E1 or CYP2A activities. Overall, our findings indicate that A and E2 have the potential to modify the catalytic activities of porcine CYP2E1 in vitro. However, the significance of this modification for skatole metabolism in vivo is questionable. (c) 2006 Elsevier Ltd. All rights reserved

Keywords

Androstenone; 17β-Oestradiol; Testosterone; Porcine microsomes; CYP2E1; CYP2A

Published in

Food and Chemical Toxicology
2007, Volume: 45, number: 4, pages: 676-681
Publisher: PERGAMON-ELSEVIER SCIENCE LTD

SLU Authors

• Zamaratskaia, Galia

  • Department of Molecular Sciences, Swedish University of Agricultural Sciences
    

• Lundström, Kerstin

  • Department of Molecular Sciences, Swedish University of Agricultural Sciences
    

UKÄ Subject classification

Animal and Dairy Science
Veterinary Science


Publication identifier

DOI: https://doi.org/10.1016/j.fct.2006.10.023

Permanent link to this page (URI)

https://res.slu.se/id/publ/16554