Simmons P S, Miles J M, Gerich J E, Haymond M W
J Clin Invest. 1984 Feb;73(2):412-20. doi: 10.1172/JCI111227.
Prolonged exposure to glucocorticoids in pharmacologic amounts results in muscle wasting, but whether changes in plasma cortisol within the physiologic range affect amino acid and protein metabolism in man has not been determined. To determine whether a physiologic increase in plasma cortisol increases proteolysis and the de novo synthesis of alanine, seven normal subjects were studied on two occasions during an 8-h infusion of either hydrocortisone sodium succinate (2 micrograms/kg X min) or saline. The rate of appearance (Ra) of leucine and alanine were estimated using [2H3]leucine and [2H3]alanine. In addition, the Ra of leucine nitrogen and the rate of transfer of leucine nitrogen to alanine were estimated using [15N]leucine. Plasma cortisol increased (10 +/- 1 to 42 +/- 4 micrograms/dl) during cortisol infusion and decreased (14 +/- 2 to 10 +/- 2 micrograms/dl) during saline infusion. No change was observed in plasma insulin, C-peptide, or glucagon during either saline or cortisol infusion. Plasma leucine concentration increased more (P less than 0.05) during cortisol infusion (120 +/- 1 to 203 +/- 21 microM) than saline (118 +/- 8 to 154 +/- 4 microM) as a result of a greater (P less than 0.01) increase in its Ra during cortisol infusion (1.47 +/- 0.08 to 1.81 +/- 0.08 mumol/kg X min for cortisol vs. 1.50 +/- 0.08 to 1.57 +/- 0.09 mumol/kg X min). Leucine nitrogen Ra increased (P less than 0.01) from 2.35 +/- 0.12 to 3.46 +/- 0.24 mumol/kg X min, but less so (P less than 0.05) during saline infusion (2.43 +/- 0.17 to 2.84 +/- 0.15 mumol/kg X min, P less than 0.01). Alanine Ra increased (P less than 0.05) during cortisol infusion but remained constant during saline infusion. During cortisol, but not during saline infusion, the rate and percentage of leucine nitrogen going to alanine increased (P less than 0.05). Thus, an increase in plasma cortisol within the physiologic range increases proteolysis and the de novo synthesis of alanine, a potential gluconeogenic substrate. Therefore, physiologic changes in plasma cortisol play a role in the regulation of whole body protein and amino acid metabolism in man.
长期大量使用糖皮质激素会导致肌肉萎缩，但生理范围内的血浆皮质醇变化是否会影响人体的氨基酸和蛋白质代谢尚未确定。为了确定血浆皮质醇的生理性增加是否会增加蛋白质水解以及丙氨酸的从头合成，对7名正常受试者在8小时内分别输注琥珀酸钠氢化可的松（2微克/千克×分钟）或生理盐水的两个时间段进行了研究。使用[2H3]亮氨酸和[2H3]丙氨酸估计亮氨酸和丙氨酸的出现率（Ra）。此外，使用[15N]亮氨酸估计亮氨酸氮的Ra以及亮氨酸氮向丙氨酸的转移率。皮质醇输注期间血浆皮质醇增加（从10±1微克/分升降至42±4微克/分升），生理盐水输注期间降低（从14±2微克/分升降至10±2微克/分升）。在生理盐水或皮质醇输注期间，血浆胰岛素、C肽或胰高血糖素均未观察到变化。由于皮质醇输注期间其Ra增加幅度更大（P＜0.01），皮质醇输注期间血浆亮氨酸浓度增加幅度（P＜0.05）大于生理盐水输注期间（皮质醇输注时从120±1微摩尔/升升至203±21微摩尔/升，生理盐水输注时从118±8微摩尔/升升至154±4微摩尔/升；皮质醇输注时为1.47±0.08至1.81±0.08微摩尔/千克×分钟，生理盐水输注时为1.50±0.08至1.57±0.09微摩尔/千克×分钟）。亮氨酸氮Ra从2.35±0.12微摩尔/千克×分钟增加到3.46±0.24微摩尔/千克×分钟（P＜0.01），但生理盐水输注期间增加幅度较小（P＜0.05，从2.43±0.17微摩尔/千克×分钟增加到2.84±0.15微摩尔/千克×分钟，P＜0.01）。丙氨酸Ra在皮质醇输注期间增加（P＜0.05），但在生理盐水输注期间保持不变。在皮质醇输注期间而非生理盐水输注期间，亮氨酸氮进入丙氨酸的速率和百分比增加（P＜0.05）。因此，生理范围内的血浆皮质醇增加会增加蛋白质水解以及丙氨酸的从头合成，丙氨酸是一种潜在的糖异生底物。所以，血浆皮质醇的生理变化在人体全身蛋白质和氨基酸代谢的调节中起作用。
