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首页> 外文期刊>Life sciences >Modulation of cholesterol 7alpha-hydroxylase and sterol 27-hydroxylase activities by steroids and physiological conditions in hamster.
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Modulation of cholesterol 7alpha-hydroxylase and sterol 27-hydroxylase activities by steroids and physiological conditions in hamster.

机译：仓鼠体内类固醇和生理条件对胆固醇7α-羟化酶和固醇27-羟化酶活性的调节。

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Our purpose was to examine the in vitro modulation of liver mitochondrial sterol 27-hydroxylase (S27OHase) and microsomal cholesterol 7alpha-hydroxylase (CH7alphaOHase) activities by certain drugs, sterols, oxysterols and bile acids, and to compare the influence of sex, age, diet and cholestyramine on these activities, in the hamster. In vitro, 7beta-hydroxycholesterol and 5alpha-cholestan-3beta-ol (cholestanol) were strong inhibitors (at 2 microM) of both enzyme activities, while 5beta-cholestan-3alpha-ol (epicoprostanol, 2 microM) and cyclosporin A (20 microM) inhibited S27OHase, but not CH7alphaOHase. These data suggest that a hydroxyl group at the 7alpha position is not required to inhibit CH7alphaOHase and that the presence of an aliphatic CH2-CH-(CH3)2 chain appears to be structurally important for S27OHase activity. Both enzyme activities remained unchanged by hyodeoxycholic acid (40 or 80 microM) while epicoprostanol inhibited only S27OHase and chenodeoxycholic acid only CH7alphaOHase. Adult (9-week old) male or female hamsters displayed similar S27OHase activity but the CH7alphaOHase activity was lower in females than in males, suggesting that the neutral bile acid pathway has a less important role in females. In male hamsters, S27OHase activity did not change with age, while CH7alphaOHase activity significantly increased (one-year vs 9-week old). A semi-purified sucrose-rich (lithogenic) diet significantly lowered both enzyme activities compared to the commercial diet. Cholestyramine induced a stimulation of both enzymes, slightly more vigorously however for the key enzyme involved in the neutral pathway. Taken together, these data indicate that the two enzymes are separately regulated and that certain drugs or steroid compounds can be useful for specifically inhibiting or stimulating the neutral or acidic bile acid pathway.
机译：我们的目的是研究某些药物，固醇，羟固醇和胆汁酸对肝线粒体固醇27-羟化酶（S27OHase）和微粒体胆固醇7α-羟化酶（CH7alphaOHase）活性的体外调节作用，并比较性别，年龄，饮食和消胆胺对这些活动的影响，在仓鼠中。在体外，7beta-羟基胆固醇和5alpha-cholestan-3beta-ol（胆固醇）是两种酶活性的强抑制剂（2 microM），而5beta-cholestan-3alpha-ol（epicoprostanol，2 microM）和环孢菌素A（20 microM） ）抑制S27OHase，但不抑制CH7alphaOHase。这些数据表明，不需要7alpha位置的羟基来抑制CH7alphaOHase，脂族CH2-CH-（CH3）2链的存在对于S27OHase活性似乎在结构上很重要。猪去氧胆酸（40或80 microM）的两种酶活性均保持不变，而表皮前列腺素仅抑制S27OHase，鹅去氧胆酸仅抑制CH7alphaOHase。成年（9周龄）雄性或雌性仓鼠显示出相似的S27OHase活性，但雌性中的CH7alphaOHase活性低于雄性，这表明中性胆汁酸途径在雌性中的作用较小。在雄性仓鼠中，S27OHase活性不会随年龄而变化，而CH7alphaOHase活性则显着增加（一年对9周龄）。与商业饮食相比，半纯化的富含蔗糖的饮食（岩浆形成）显着降低了两种酶的活性。胆甾胺诱导两种酶的刺激，但是对于参与中性途径的关键酶的刺激稍强一些。综上所述，这些数据表明这两种酶是分别调节的，某些药物或类固醇化合物可用于特异性抑制或刺激中性或酸性胆汁酸途径。

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