性别依赖性的 CYP3A 活性被去甲肾上腺素能系统中的 GR 间接修饰。
Gender-dependent activity of CYP3A is indirectly modified by GR in the noradrenergic system.
机构信息
Department of Pharmacokinetics and Drug Metabolism, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, PL 31-343 Kraków, Poland.
出版信息
Pharmacol Rep. 2013;65(5):1431-4. doi: 10.1016/s1734-1140(13)71503-2.
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.
背景
去甲肾上腺素系统参与肝脏细胞色素 P450 活性的调节。我们研究了去甲肾上腺素系统中糖皮质激素受体选择性缺失对小鼠肝 CYP3A 同工酶活性的影响。
方法
通过测量肝微粒体中睾酮 6β-羟化的速率来研究 CYP3A 的活性。
结果
在突变小鼠中，CYP3A 的活性在雌性小鼠中降低至对照的 68%，而在雄性小鼠中则保持不变。慢性束缚应激仅增加突变小鼠中的 CYP3A 活性。
结论
在青春期期间，糖皮质激素受体可能通过去甲肾上腺素系统间接调节小鼠 CYP3A 的总基础活性。
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