Jansen H, van Tol A, Auwerx J, Skretting G, Staels B
Department of Internal Medicine III, Erasmus University, Rotterdam, Netherlands.
Biochim Biophys Acta. 1992 Oct 30;1128(2-3):181-5. doi: 10.1016/0005-2760(92)90305-f.
Rats were treated with hydrocortisone, dexamethasone or triamcinolone for 4 days. The effect of treatment on hepatic lipase and lecithin:cholesterol acyltransferase (LCAT) mRNA levels and catalytic activities was determined. Hepatic lipase mRNA was not affected by hydrocortisone, but was decreased after dexamethasone (-28%) and triamcinolone (-54%). Hepatic lipase activity followed the same pattern, it was not affected by hydrocortisone and lowered by dexamethasone (-38%) and triamcinolone (-70%). The LCAT mRNA level in the liver was also not affected by hydrocortisone, but increased upon treatment with dexamethasone (+22%) and triamcinolone (+72%). Plasma LCAT, determined with an excess exogenous substrate (designated LCAT-II), tended to decrease after hydrocortisone treatment (-11%) and was higher after dexamethasone (+21%) and triamcinolone (+22%). The plasma cholesterol esterification rate (designated LCAT-I), determined by incubation of the plasma at 37 degrees C, followed the same pattern. The activity ratio of hepatic lipase/LCAT-II decreased from 1 in the controls to 0.51 after dexamethasone and 0.25 in the triamcinolone-treated animals. The plasma HDL cholesterol concentration in the different groups changed oppositely to the hepatic lipase/LCAT activity ratio. It is concluded that HDL cholesterol is raised by synthetic glucocorticoids due, among other factors, to a lowered hepatic lipase and an increased plasma LCAT activity. The influence of glucocorticoids on these enzymes is, at least partly, explained by the effects on the hepatic mRNA contents.
用氢化可的松、地塞米松或曲安西龙对大鼠进行4天的治疗。测定治疗对肝脂肪酶和卵磷脂胆固醇酰基转移酶(LCAT)mRNA水平及催化活性的影响。氢化可的松对肝脂肪酶mRNA无影响,但地塞米松(-28%)和曲安西龙(-54%)处理后其水平降低。肝脂肪酶活性呈现相同模式,氢化可的松对其无影响,地塞米松(-38%)和曲安西龙(-70%)使其降低。肝脏中LCAT mRNA水平也不受氢化可的松影响,但地塞米松(+22%)和曲安西龙(+72%)处理后升高。用过量外源性底物测定的血浆LCAT(称为LCAT-II),氢化可的松治疗后有降低趋势(-11%),地塞米松(+21%)和曲安西龙(+22%)治疗后升高。通过在37℃孵育血浆测定的血浆胆固醇酯化率(称为LCAT-I)呈现相同模式。肝脂肪酶/LCAT-II的活性比从对照组的1降至地塞米松处理后的0.51和曲安西龙处理动物的0.25。不同组血浆高密度脂蛋白胆固醇浓度的变化与肝脂肪酶/LCAT活性比相反。结论是,合成糖皮质激素可使高密度脂蛋白胆固醇升高,这至少部分是由于肝脂肪酶降低和血浆LCAT活性增加。糖皮质激素对这些酶的影响至少部分可通过对肝脏mRNA含量的作用来解释。