Lehoux J G, Lefebvre A
Department of Biochemistry, Faculty of Medicine, University of Sherbrooke, Quebec, Canada.
J Mol Endocrinol. 1991 Jun;6(3):223-30. doi: 10.1677/jme.0.0060223.
Low-density lipoprotein (LDL) receptor mRNA was found in both rat and hamster adrenals. Within 30 min after ACTH administration a significant increase in the levels of both LDL receptor and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) mRNAs was observed in rat adrenals; these levels remained increased for up to 240 min. The increase in the levels of LDL receptor and HMG-CoA reductase mRNAs produced by ACTH was reduced by co-administration of aminoglutethimide while, at the same time, the adrenal cholesterol content of rats treated with both aminoglutethimide and ACTH was significantly increased compared with that in groups treated with ACTH alone. Cycloheximide also induced increased levels of rat adrenal mRNAs for LDL receptor and HMG-CoA reductase, but this effect was not additive with that of ACTH. These results suggest that, in the rat, the short-term effect of ACTH on the levels of mRNAs for the LDL receptor and HMG-CoA reductase is similarly controlled and might be mediated through changes in the adrenal cholesterol content. In the hamster adrenal, however, no significant fluctuations were found in the level of LDL receptor mRNA, although a marked increase was found in the level of HMG-CoA reductase mRNA, 2 h after ACTH administration. This indicates that an important effect of ACTH on cholesterol metabolism in the hamster adrenal is at the level of HMG-CoA reductase. In the hamster, therefore, where the main source of cholesterol for the adrenal gland is de-novo synthesis, it seems that a complex mechanism is involved in the control of LDL receptor gene expression.
在大鼠和仓鼠的肾上腺中均发现了低密度脂蛋白（LDL）受体mRNA。给予促肾上腺皮质激素（ACTH）后30分钟内，在大鼠肾上腺中观察到LDL受体和3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）mRNA水平显著升高；这些水平在长达240分钟内持续升高。同时给予氨鲁米特可降低ACTH引起的LDL受体和HMG-CoA还原酶mRNA水平的升高，而与此同时，与单独给予ACTH的组相比，同时给予氨鲁米特和ACTH的大鼠肾上腺胆固醇含量显著增加。放线菌酮也可诱导大鼠肾上腺中LDL受体和HMG-CoA还原酶mRNA水平升高，但这种作用与ACTH的作用无相加性。这些结果表明，在大鼠中，ACTH对LDL受体和HMG-CoA还原酶mRNA水平的短期作用受到类似的调控，可能是通过肾上腺胆固醇含量的变化介导的。然而，在仓鼠肾上腺中，给予ACTH 2小时后，LDL受体mRNA水平未发现明显波动，尽管HMG-CoA还原酶mRNA水平显著升高。这表明ACTH对仓鼠肾上腺胆固醇代谢的重要作用是在HMG-CoA还原酶水平。因此，在仓鼠中，肾上腺胆固醇的主要来源是从头合成，似乎在LDL受体基因表达的调控中涉及一种复杂的机制。
