Balasubramaniam S, Goldstein J L, Faust J R, Brunschede G Y, Brown M S
J Biol Chem. 1977 Mar 10;252(5):1771-9.
In the adrenal gland of the rat, the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase, the rate-controlling enzyme of cholesterol synthesis, is shown to be regulated by cholesteerol carried in plasma lipoproteins. When plasma cholesterol levels were lowered 90% by administration of the drug 4-aminopyrazolopyrimidine, the cholesteryl ester content of the adrenal gland declined by more than 90% and this was associated with a 150- to 200-fold increase in the activity of adrenal 3-hydroxy-3-methylglutaryl coenzyme A reductase and a 30-fold increase in cholesterol synthesis from [14C]acetate. The subsequent intravenous infusion of cholesterol contained in either rat or human high density or low density lipoproteins restored the adrenal content of cholesteryl esters and reduced the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase to basal levels. The depletion of adrenal cholesteryl esters and the enhancement in the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase that occurred in the 4-aminopyrazolopyrimidine-treated rat required the action of adrenocorticotropic hormone (ACTH) since neither was observed when ACTH secretion was blocked by administration of dexamethasone. The current data indicate that the low rate of cholesterol synthesis normally observed in the rat adrenal gland is due to a suppression of the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase that is mediated by plasma lipoproteins.
在大鼠肾上腺中，胆固醇合成的限速酶3-羟基-3-甲基戊二酰辅酶A还原酶的活性受血浆脂蛋白携带的胆固醇调节。当通过给予药物4-氨基吡唑并嘧啶使血浆胆固醇水平降低90%时，肾上腺的胆固醇酯含量下降超过90%，这与肾上腺3-羟基-3-甲基戊二酰辅酶A还原酶活性增加150至200倍以及[14C]乙酸盐合成胆固醇增加30倍有关。随后静脉输注大鼠或人高密度或低密度脂蛋白所含的胆固醇，可使肾上腺胆固醇酯含量恢复，并使3-羟基-3-甲基戊二酰辅酶A还原酶活性降至基础水平。在4-氨基吡唑并嘧啶处理的大鼠中发生的肾上腺胆固醇酯耗竭和3-羟基-3-甲基戊二酰辅酶A还原酶活性增强需要促肾上腺皮质激素（ACTH）的作用，因为当通过给予地塞米松阻断ACTH分泌时，两者均未观察到。目前的数据表明，正常情况下在大鼠肾上腺中观察到的低胆固醇合成速率是由于血浆脂蛋白介导的3-羟基-3-甲基戊二酰辅酶A还原酶活性受到抑制。
