Roberts A J, Gallaher E J, Keith L D
Research Service, Department of Veterans Affairs Medical Center, Portland, OR 97201.
Neuroendocrinology. 1993 Sep;58(3):303-9. doi: 10.1159/000126554.
Adrenalectomy is frequently used to deplete adrenocortical hormones in physiological and receptor-binding studies in animals. However, this procedure is irreversible, removes both the cortex and medulla, and produces many negative side effects such as hypotension and hypoglycemia. Aminoglutethimide is a steroid synthesis inhibitor which depletes adrenocortical hormones without these negative effects. However, aminoglutethimide itself has been shown to produce behavioral and physiological deficits. In the present experiments, dose-response relationships were determined for the effects of aminoglutethimide on corticosterone levels, motor coordination, and body temperature in C57 and DBA mice. Aminoglutethimide (5.4-54 mg/kg) inhibited the increase in plasma corticosterone concentrations normally observed in response to restraint stress. Only at higher doses (170-1,000 mg/kg) were rotarod performance and body temperature affected. The corticosterone response to restraint stress recovered fully between 12 and 24 h after aminoglutethimide. In the present study, doses of aminoglutethimide were found that temporarily inhibit stressed corticosterone release without producing motor deficits and temperature decreases. These results indicate that aminoglutethimide is a potential substitute for adrenalectomy in studies on the effects of removal of adrenocortical hormones.
在动物的生理学和受体结合研究中，肾上腺切除术常被用于消耗肾上腺皮质激素。然而，该手术是不可逆的，会同时切除皮质和髓质，并产生许多负面副作用，如低血压和低血糖。氨鲁米特是一种类固醇合成抑制剂，它能消耗肾上腺皮质激素而无这些负面影响。然而，氨鲁米特本身已被证明会导致行为和生理缺陷。在本实验中，测定了氨鲁米特对C57和DBA小鼠皮质酮水平、运动协调性和体温影响的剂量反应关系。氨鲁米特（5.4 - 54毫克/千克）抑制了通常在应激状态下观察到的血浆皮质酮浓度的升高。只有在较高剂量（170 - 1000毫克/千克）时，转棒试验表现和体温才会受到影响。氨鲁米特作用后12至24小时内，皮质酮对应激的反应完全恢复。在本研究中，发现了能暂时抑制应激状态下皮质酮释放而不产生运动缺陷和体温下降的氨鲁米特剂量。这些结果表明，在关于去除肾上腺皮质激素影响的研究中，氨鲁米特是肾上腺切除术的一种潜在替代方法。
