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

BackgroundThe 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 theCYP3Aisoforminmouse liver.MethodsThe activity of CYP3A was studied by measuring the rate of testosterone 6β-hydroxylation in liver microsomes.ResultsIn 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.ConclusionsThe total basal activity of mouse CYP3A may be indirectly modulated by the glucocorticoid receptor in the noradrenergic system during a pubertal period.