Baumgartner A, Heyne A, Campos-Barros A, Köhler R, Müller F, Meinhold H, Rommelspacher H, Wolffgramm J
Department of Psychiatry, Klinikum Steglitz, Free University of Berlin, Germany.
Alcohol Clin Exp Res. 1994 Apr;18(2):295-304. doi: 10.1111/j.1530-0277.1994.tb00017.x.
Thyroxine (T4), triiodothyronine (T3) concentrations, and the activities of the three deiodinase isoenzymes were measured in different brain regions and peripheral tissues of rats. According to an animal model of alcohol addiction, "behaviorally" dependent rats having lost control over their intake of ethanol were compared with alcohol-naive controls and ethanol-experienced, but "controlled" consumers. The two kinds of alcohol-experienced rats were investigated either 24 hr or 3 months after ethanol withdrawal. The results of these four groups were compared with those of an ethanol-naive control group. During withdrawal, the activities of type II 5'-deiodinase (which catalyzes deiodination of T4 and T3 in the CNS) in both the "behaviorally dependent" rats and the "controlled drinkers" were significantly lower than in the alcohol-naive controls in the frontal cortex, parieto-occipital cortex, hippocampus, and striatum, but not in the cerebellum or pituitary. Probably as a result, the tissue concentrations of T4 were higher in areas of the CNS in the groups exposed to alcohol. However, the T3 concentrations were normal. No relevant differences were seen between the activities of type III 5-deiodinase (which catalyzes the further deiodination of T3) observed in these groups. After 3 months of abstinence, the type II 5'-deiodinase activities had almost returned to normal in both "controlled drinkers" and "behaviorally dependent" animals, whereas type III 5-deiodinase activity was inhibited, possibly to maintain physiological concentrations of T3 during abstinence. Indeed, the tissue levels of T3 were normal in the areas of the CNS, and the T4 levels were still elevated. However, the liver concentrations of T3 and T4 were significantly lower in the "behaviourally dependent" animals than in the "controlled" drinkers after 3 months of abstinence, whereas no differences were found between the T4 and T3 concentrations in the areas of the CNS investigated in the two groups exposed to ethanol. These results suggest that chronic administration of ethanol affects intracellular thyroid hormone metabolism in both rat CNS and liver in the highly complex manner. No direct evidence of ethanol-induced enhancement of tissue uptake or concentrations was obtained. However, taking into account the numerous similarities between the clinical picture of hyperthyroidism and the symptomatology of alcoholism, it may be hypothesized that ethanol may directly influence any step in the as yet unknown biochemical cascade of thyroid hormone function.
在大鼠的不同脑区和外周组织中测量了甲状腺素（T4）、三碘甲状腺原氨酸（T3）的浓度以及三种脱碘酶同工酶的活性。根据酒精成瘾动物模型，将对乙醇摄入失去控制的“行为依赖型”大鼠与未接触过酒精的对照组以及有乙醇接触经历但能“控制”饮酒量的大鼠进行比较。对这两类有乙醇接触经历的大鼠在戒断乙醇24小时或3个月后进行研究。将这四组的结果与未接触乙醇的对照组的结果进行比较。在戒断期间，“行为依赖型”大鼠和“控制饮酒者”中II型5'-脱碘酶（催化中枢神经系统中T4和T3的脱碘作用）在额叶皮质、顶枕叶皮质、海马体和纹状体中的活性均显著低于未接触酒精的对照组，但在小脑或垂体中则不然。可能因此，接触酒精的组中中枢神经系统区域的T4组织浓度较高。然而，T3浓度正常。在这些组中观察到的III型5-脱碘酶（催化T3进一步脱碘）的活性之间没有相关差异。在戒断3个月后，“控制饮酒者”和“行为依赖型”动物的II型5'-脱碘酶活性几乎恢复正常，而III型5-脱碘酶活性受到抑制，这可能是为了在戒断期间维持T3的生理浓度。实际上，中枢神经系统区域的T3组织水平正常，T4水平仍然升高。然而，在戒断3个月后，“行为依赖型”动物肝脏中的T3和T4浓度显著低于“控制饮酒者”，而在两组接触乙醇的大鼠所研究的中枢神经系统区域中，T4和T3浓度之间没有差异。这些结果表明，长期给予乙醇以高度复杂的方式影响大鼠中枢神经系统和肝脏中的细胞内甲状腺激素代谢。未获得乙醇诱导组织摄取或浓度增加的直接证据。然而，考虑到甲状腺功能亢进的临床表现与酒精中毒症状之间的众多相似之处，可以推测乙醇可能直接影响甲状腺激素功能尚未明确的生化级联反应中的任何一个步骤。
