Wand G S
Division of Endocrinology and Metabolism, Johns Hopkins University, Baltimore, Maryland 21205.
Endocrinology. 1989 Jan;124(1):518-26. doi: 10.1210/endo-124-1-518.
The stimulatory effects of ethanol administration on the hypothalamic-pituitary-adrenal (HPA) axis were investigated in the long sleep (LS) and short sleep (SS) lines of mice, selectively bred for differences in sensitivity to ethanol. To characterize the effects of ethanol exposure on levels of anterior pituitary pro-ACTH/endorphin mRNA, animals were treated with ethanol for either 4 or 7 days. Northern analyses of total RNA extracted from anterior pituitary indicated that ethanol-treated SS mice had 1.5-fold higher pro-ACTH/endorphin mRNA levels on day 4 and 2.5-fold higher mRNA levels on day 7 than SS control mice. Although ethanol-treated LS mice had 4-fold higher pro-ACTH/endorphin mRNA levels on day 4 compared to those in control LS mice, by day 7 pro-ACTH/endorphin mRNA levels in ethanol-treated LS mice were 40% less than LS control levels. Quantitation of pro-ACTH/endorphin-related peptide biosynthesis was determined by immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis of extracts from [35S]methionine-labeled anterior pituitary explants. Ethanol treatment for 7 days increased pro-ACTH/endorphin biosynthesis in SS mice, but decreased pro-ACTH/endorphin biosynthesis in LS mice. These results parallel the effect of ethanol on pro-ACTH/endorphin mRNA levels. Serum corticosterone levels also paralleled pro-ACTH/endorphin production in both lines of mice. In summary, ethanol acutely activates the HPA axis in SS mice, and this activation is sustained after repeated ethanol administration. In contrast, LS mice have initial activation of the HPA axis, which attenuates after repeated ethanol exposure. LS and SS mice may be appropriate models for understanding the mechanism(s) responsible for the differential activation of the HPA axis by ethanol and the development of pseudo-Cushing's syndrome in man.
在对乙醇敏感性存在差异而经选择性培育的长睡眠（LS）和短睡眠（SS）品系小鼠中，研究了给予乙醇对下丘脑 - 垂体 - 肾上腺（HPA）轴的刺激作用。为了表征乙醇暴露对垂体前叶促肾上腺皮质激素原/内啡肽mRNA水平的影响，对动物进行了4天或7天的乙醇处理。对从垂体前叶提取的总RNA进行的Northern分析表明，乙醇处理的SS小鼠在第4天促肾上腺皮质激素原/内啡肽mRNA水平比SS对照小鼠高1.5倍，在第7天mRNA水平高2.5倍。尽管乙醇处理的LS小鼠在第4天促肾上腺皮质激素原/内啡肽mRNA水平比对照LS小鼠高4倍，但到第7天，乙醇处理的LS小鼠促肾上腺皮质激素原/内啡肽mRNA水平比LS对照水平低40%。通过对[35S]甲硫氨酸标记的垂体前叶外植体提取物进行免疫沉淀和十二烷基硫酸钠 - 聚丙烯酰胺凝胶电泳，对促肾上腺皮质激素原/内啡肽相关肽生物合成进行了定量分析。7天的乙醇处理增加了SS小鼠促肾上腺皮质激素原/内啡肽的生物合成，但降低了LS小鼠促肾上腺皮质激素原/内啡肽的生物合成。这些结果与乙醇对促肾上腺皮质激素原/内啡肽mRNA水平的影响一致。血清皮质酮水平在这两个品系小鼠中也与促肾上腺皮质激素原/内啡肽的产生一致。总之，乙醇急性激活SS小鼠的HPA轴，并且在重复给予乙醇后这种激活得以持续。相比之下，LS小鼠HPA轴最初被激活，但在重复乙醇暴露后减弱。LS和SS小鼠可能是理解乙醇对HPA轴不同激活机制以及人类假性库欣综合征发生机制的合适模型。
