Burczynski J M, Hayes J R, Voigt J M, Longhurst P A, Colby H D
Albany College of Pharmacy, 106 New Scotland Avenue, Albany, New York 12208, USA.
J Endocrinol. 2001 Feb;168(2):333-8. doi: 10.1677/joe.0.1680333.
Previous studies demonstrated high levels of lipid peroxidation (LP) in the guinea pig adrenal cortex. The present studies were done to determine if adrenal LP activity was influenced by ACTH, the major hormonal regulator of the gland. Guinea pigs were treated with ACTH for 1, 3 or 7 days. In addition, some guinea pigs received ACTH for 7 days and were killed 3 or 7 days later. After treatment, adrenal microsomal fractions were prepared and incubated in vitro with 1 mM ferrous sulfate to initiate LP. ACTH treatment caused a progressive decrease in adrenal LP; activity was almost totally inhibited within 3 days. The inhibitory effects of ACTH on LP were dose-dependent. Following cessation of ACTH treatment, adrenal LP gradually returned toward control levels. Microsomal concentrations of linoleic acid, a major substrate for adrenal LP, were increased by ACTH administration and then also returned to control levels after cessation of treatment. There were no significant changes in adrenal alpha-tocopherol or beta-carotene concentrations resulting from ACTH treatment. The results indicate that ACTH has a role in the regulation of adrenal LP. The actions of ACTH cannot be attributed to an increase in adrenal content of the antioxidants, alpha-tocopherol and beta-carotene, or to a decrease in LP substrate. The actions of ACTH to inhibit LP may contribute to an increase in adrenal hormone production by protecting steroidogenic enzymes from peroxidative degradation.
先前的研究表明,豚鼠肾上腺皮质中脂质过氧化(LP)水平较高。本研究旨在确定肾上腺LP活性是否受促肾上腺皮质激素(ACTH)影响,ACTH是该腺体的主要激素调节因子。对豚鼠进行1、3或7天的ACTH处理。此外,一些豚鼠接受7天的ACTH处理,并在3天或7天后处死。处理后,制备肾上腺微粒体部分,并在体外与1 mM硫酸亚铁一起孵育以启动LP。ACTH处理导致肾上腺LP逐渐降低;3天内活性几乎完全被抑制。ACTH对LP的抑制作用呈剂量依赖性。停止ACTH处理后,肾上腺LP逐渐恢复至对照水平。ACTH给药可增加肾上腺LP的主要底物亚油酸的微粒体浓度,处理停止后其也恢复至对照水平。ACTH处理未导致肾上腺α-生育酚或β-胡萝卜素浓度发生显著变化。结果表明,ACTH在肾上腺LP的调节中起作用。ACTH的作用不能归因于肾上腺抗氧化剂α-生育酚和β-胡萝卜素含量的增加,也不能归因于LP底物的减少。ACTH抑制LP的作用可能通过保护类固醇生成酶免受过氧化降解,从而有助于肾上腺激素产生的增加。