Lehoux J G, Lefebvre A, Bélisle S, Bellabarba D
J Steroid Biochem. 1986 Jan;24(1):325-9. doi: 10.1016/0022-4731(86)90074-9.
In this study we have determined the effect of ACTH on the activity of HMG-CoA reductase in microsomes of hamster adrenals. Cycloheximide was used to study the dependence of the increased enzyme activity by ACTH on de novo protein synthesis. Microsomes were prepared and preincubated with and without NaF and in the presence or absence of phosphorylase phosphatase in order to differentiate between expressed (McNaF) and total (McPP) activity. ACTH induced (after 120 and 180 min) significant increases in HMG-CoA reductase activity with a latent period of 60 min for both McNaF and McPP preparations. Cycloheximide alone decreased the activity of the reductase and the coadministration of cycloheximide + ACTH caused a greater loss of activity. Also, both treatments produced an accumulation of free cholesterol in adrenals suggesting an increased turnover of the reductase by these substances. Preincubation of microsomes at 37 degrees C enhanced per se HMG-CoA reductase activity, but the relative increase produced by ACTH treatments or endogenous ACTH remained essentially the same. In conclusion, under experimental conditions used, the enhancement of HMG-CoA reductase activity produced by ACTH seem to be due to increased enzyme synthesis.
在本研究中，我们测定了促肾上腺皮质激素（ACTH）对仓鼠肾上腺微粒体中羟甲基戊二酸单酰辅酶A（HMG-CoA）还原酶活性的影响。使用放线菌酮来研究ACTH所引起的酶活性增加对从头合成蛋白质的依赖性。制备微粒体，并在有或没有氟化钠（NaF）以及有或没有磷酸化酶磷酸酶存在的情况下进行预孵育，以便区分表达的（McNaF）和总的（McPP）活性。ACTH诱导（120分钟和180分钟后）HMG-CoA还原酶活性显著增加，对于McNaF和McPP制剂，潜伏期均为60分钟。单独使用放线菌酮会降低还原酶的活性，而放线菌酮与ACTH共同给药会导致更大的活性损失。此外，两种处理都会导致肾上腺中游离胆固醇的积累，这表明这些物质会增加还原酶的周转。在37℃下对微粒体进行预孵育本身会增强HMG-CoA还原酶的活性，但ACTH处理或内源性ACTH所产生的相对增加基本保持不变。总之，在所使用的实验条件下，ACTH所引起的HMG-CoA还原酶活性增强似乎是由于酶合成增加所致。
