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Published on: January 20, 2015
Gender-dependent activity of CYP3A is indirectly modified by GR in the noradrenergic system
Marta Kot1, Grzegorz Kreiner, Piotr Chmielarz
1Department of Pharmacokinetics and Drug Metabolism, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, PL 31-343 Kraków, Poland. kot@if-pan.krakow.pl.
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.
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