Gender-dependent activity of CYP3A is indirectly modified by GR in the noradrenergic system

Pharmacol Rep. 2013;65(5):1431-4. doi: 10.1016/s1734-1140(13)71503-2.

Abstract

Background: The noradrenergic system is involved in the regulation of cytochrome P450 activity in the liver. We investigated the effect of selective ablation of the glucocorticoid receptor in the noradrenergic systemon the activity of the CYP3A isoform in mouse liver.

Methods: The activity of CYP3A was studied by measuring the rate of testosterone 6β-hydroxylation in liver microsomes.

Results: In mutant mice, the activity of CYP3A was reduced to 68% of the control in females, but remained unchanged in males. Chronic restraint stress increased CYP3A activity in mutant mice only.

Conclusions: The total basal activity of mouse CYP3A may be indirectly modulated by the glucocorticoid receptor in the noradrenergic system during a pubertal period.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biotransformation
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 Enzyme System / metabolism*
  • Disease Models, Animal
  • Female
  • Hydroxylation
  • Kinetics
  • Liver / enzymology*
  • Male
  • Mice
  • Mice, Mutant Strains
  • Microsomes, Liver / enzymology
  • Norepinephrine / metabolism*
  • Receptors, Glucocorticoid / genetics
  • Receptors, Glucocorticoid / metabolism*
  • Restraint, Physical
  • Sex Factors
  • Stress, Psychological / enzymology
  • Stress, Psychological / genetics
  • Testosterone / metabolism

Substances

  • NR3C1 protein, mouse
  • Receptors, Glucocorticoid
  • Testosterone
  • Cytochrome P-450 Enzyme System
  • CYP3A protein, mouse
  • Cytochrome P-450 CYP3A
  • Norepinephrine