Lehoux J G, Lefebvre A, Bélisle S, Bellabarba D
Faculty of Medicine, University of Sherbrooke, Canada.
Mol Cell Endocrinol. 1990 Feb 12;69(1):41-9. doi: 10.1016/0303-7207(90)90087-o.
4-Aminopyrazolopyrimidine (4-APP) treatments to rats for 3 days induced 2-fold increase of circulating ACTH and 11-fold increase of adrenal 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase mRNA compared to NaCl-treated controls. This in vivo model was used to study the effect of the suppression of ACTH secretion on the adrenal HMG-CoA reductase mRNA level. Dexamethasone (Dex) administration to 4-APP-treated rats caused a rapid and parallel decline of the levels of plasma ACTH and adrenal HMG-CoA reductase mRNA to 50% within 2.5 h, whereas the free and esterified cholesterol content was increased 5 and 9.4 times respectively. These changes could be counteracted by the co-administration of ACTH with Dex. Aminoglutethimide (AG) administration to 4-APP-treated rats, which increased the adrenal esterified cholesterol content (7.5 times), decreased the HMG-CoA reductase mRNA level (44%), despite plasma ACTH level remaining elevated. Moreover, the participation of newly synthesized protein(s) in the lowering of adrenal HMG-CoA reductase mRNA level induced by ACTH suppression is suggested by the fact that cycloheximide (Cyclo), when co-administered with AG, completely blocked the decrease of HMG-CoA reductase mRNA level, despite the plasma ACTH level decreasing by 68% and the free and esterified cholesterol content increasing 3.9 and 12.3 times, compared to 4-APP-treated rats. Furthermore, the specificity of these effects was established by the fact that the beta-actin mRNA level was not affected by the administration of either Dex, AG, Cyclo, or AG + Cyclo to 4-APP-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)
与用氯化钠处理的对照组相比，用4-氨基吡唑并嘧啶（4-APP）对大鼠进行3天处理后，循环促肾上腺皮质激素（ACTH）增加了2倍，肾上腺3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶mRNA增加了11倍。该体内模型用于研究抑制ACTH分泌对肾上腺HMG-CoA还原酶mRNA水平的影响。给用4-APP处理的大鼠注射地塞米松（Dex），导致血浆ACTH水平和肾上腺HMG-CoA还原酶mRNA水平在2.5小时内迅速且平行下降至50%，而游离胆固醇和酯化胆固醇含量分别增加了5倍和9.4倍。ACTH与Dex共同给药可抵消这些变化。给用4-APP处理的大鼠注射氨鲁米特（AG），可增加肾上腺酯化胆固醇含量（7.5倍），尽管血浆ACTH水平仍升高，但HMG-CoA还原酶mRNA水平降低了44%。此外，放线菌酮（Cyclo）与AG共同给药时，尽管与用4-APP处理的大鼠相比，血浆ACTH水平下降了68%，游离胆固醇和酯化胆固醇含量分别增加了3.9倍和12.3倍，但完全阻断了HMG-CoA还原酶mRNA水平的下降，这表明新合成的蛋白质参与了ACTH抑制诱导的肾上腺HMG-CoA还原酶mRNA水平的降低。此外，用Dex、AG、Cyclo或AG + Cyclo对用4-APP处理的大鼠给药后，β-肌动蛋白mRNA水平未受影响，从而证实了这些作用的特异性。（摘要截断于250字）
