title: Gender-dependent activity of CYP3A is indirectly modified by GR in the noradrenergic system.
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.
authors.affiliation: Department of Pharmacokinetics and Drug Metabolism, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, PL 31-343 Kraków, Poland. kot@if-pan.krakow.pl.
authors.forename: Marta
authors.initials: M
authors.lastname: Kot
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Kreiner
authors.forename: Piotr
authors.initials: P
authors.lastname: Chmielarz
authors.forename: Justyna
authors.initials: J
authors.lastname: Kuśmierczyk
authors.forename: Irena
authors.initials: I
authors.lastname: Nalepa
authors.forename: Władysława A
authors.initials: WA
authors.lastname: Daniel
mesh_terms: D000818:Animals; D001711:Biotransformation; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D006900:Hydroxylation; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008862:Microsomes, Liver / Q000201:enzymology; D009638:Norepinephrine / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism*; D012149:Restraint, Physical; D012737:Sex Factors; D013315:Stress, Psychological / Q000201:enzymology / Q000235:genetics; D013739:Testosterone / Q000378:metabolism; D008565:Membrane Proteins
chemical_list: D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System; D009638:Norepinephrine; D011965:Receptors, Glucocorticoid; D013739:Testosterone; C575863:NR3C1 protein, mouse; C496508:Cyp3a11 protein, mouse; D008565:Membrane Proteins