Jacobson L, Zurakowski D, Majzoub J A
Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA.
Endocrinology. 1997 Mar;138(3):1048-57. doi: 10.1210/endo.138.3.5011.
The mechanism by which protein malnutrition increases circulating glucocorticoids is unclear. To determine whether ACTH synthesis and secretion also increase in protein malnutrition, rats were sham adrenalectomized or adrenalectomized and replaced with varying amounts of corticosterone before dietary protein deprivation. Pair-fed rats served as controls for reduced voluntary food intake in protein-deprived rats. Dietary protein deficiency, but not pair-feeding, increased resting plasma corticosterone in sham-adrenalectomized rats. Restraint-induced ACTH secretion was not inhibited by the increased basal corticosterone levels in protein-deficient rats. When increases in corticosterone were eliminated by adrenalectomy or controlled by adrenalectomy with low level corticosterone replacement, increases in resting plasma ACTH and anterior pituitary POMC messenger RNA expression occurred with protein deprivation that could be statistically discriminated by regression analysis from changes due to caloric restriction (pair-feeding) and overt glucocorticoid feedback resistance. We conclude that protein malnutrition increases pituitary-adrenocortical activity at least in part by specifically increasing the drive for ACTH synthesis and secretion.
蛋白质营养不良增加循环糖皮质激素的机制尚不清楚。为了确定蛋白质营养不良时促肾上腺皮质激素（ACTH）的合成和分泌是否也会增加，在饮食蛋白质剥夺前，将大鼠进行假肾上腺切除术或肾上腺切除术，并给予不同剂量的皮质酮替代。配对喂养的大鼠作为蛋白质缺乏大鼠自愿食物摄入量减少的对照。饮食蛋白质缺乏而非配对喂养，增加了假肾上腺切除大鼠的静息血浆皮质酮水平。蛋白质缺乏大鼠基础皮质酮水平升高并未抑制束缚诱导的ACTH分泌。当通过肾上腺切除术消除皮质酮增加或通过低水平皮质酮替代的肾上腺切除术控制皮质酮增加时，蛋白质剥夺会导致静息血浆ACTH和垂体前叶阿黑皮素原（POMC）信使核糖核酸表达增加，通过回归分析，这种增加在统计学上可与热量限制（配对喂养）和明显的糖皮质激素反馈抵抗引起的变化区分开来。我们得出结论，蛋白质营养不良至少部分通过特异性增加ACTH合成和分泌的驱动力来增加垂体-肾上腺皮质活性。
