Wolthers T, Grøfte T, Jørgensen J O, Møller N, Vahl N, Christiansen J S, Vilstrup H
Medical Department M (Endocrinology and Diabetes), Aarhus University Hospital, Denmark.
J Clin Endocrinol Metab. 1994 May;78(5):1220-4. doi: 10.1210/jcem.78.5.7513718.
A decline in serum urea levels and urinary urea excretion is usually seen after GH administration in humans, indicating overall protein anabolism. Whether this reflects the diminished supply of alpha-amino acids for urea synthesis or a substrate-independent hepatic mechanism is unknown. To pursue this we measured the urea nitrogen synthesis rate (UNSR) and blood alanine levels before, during, and after a 4-h constant iv infusion of alanine (2 mmol/kg BW.h). UNSR was estimated hourly as urinary excretion corrected for gut hydrolysis and accumulation in total body water. The slope of the linear relationship between UNSR and circulating alanine levels represents the hepatic components of conversion of amino nitrogen and is denoted the functional hepatic nitrogen clearance (FHNC). Eight male volunteers were randomly investigated on three occasions: 1) after 12-h iv saline infusion, 2) after 12-h iv GH infusion (1 IU/h), and 3) after 2-day sc GH treatment (8 IU/day), followed by 12-h iv infusion of GH (1 IU/h). The UNSR (millimoles per h) during alanine infusion was significantly lower when the subjects were receiving GH therapy [maximum +/- SE, 133.0 +/- 6.9 (saline) vs. 96.7 +/- 11.1 (12-h GH; P < 0.01) vs. 106.5 +/- 7.5 (2-day GH; P < 0.05)]. FHNC (liters per h) was similar in all three studies [30.3 +/- 1.2 (saline) vs. 26.6 +/- 3.4 (12-h GH) vs. 27.0 +/- 2.6 (2-day GH)]. Six GH-deficient adult patients were randomly studied twice: 1) on regular daily (at 2000 h) sc GH therapy (3 IU/m2.day), and 2) after discontinuation of GH for 2 days. The UNSR during alanine infusion was likewise significantly lower when the patients were receiving GH therapy [147.7 +/- 11.7 mmol/h (no GH) vs. 123.9 +/- 9.1 mmol/h; P < 0.01]. FHNC (liters per h) values were similar in the two studies [29.2 +/- 3.8 (GH) vs. 27.5 +/- 4.5 (no GH)]. Our data confirm the anabolic action of GH and show that short term GH deprivation is associated with catabolism in terms of increased UNSR. The finding of unaltered FHNC suggests a GH-induced extrahepatic regulation of amino nitrogen conversion, rather than a substrate-independent hepatic mechanism.
在人类中，生长激素（GH）给药后通常会出现血清尿素水平和尿尿素排泄量下降，这表明整体蛋白质合成代谢。这是反映用于尿素合成的α-氨基酸供应减少，还是一种不依赖底物的肝脏机制，目前尚不清楚。为了探究这一点，我们在持续4小时静脉输注丙氨酸（2 mmol/kg体重·小时）之前、期间和之后，测量了尿素氮合成率（UNSR）和血丙氨酸水平。每小时估算一次UNSR，即校正肠道水解和全身水蓄积后的尿排泄量。UNSR与循环丙氨酸水平之间线性关系的斜率代表氨基氮转化的肝脏组成部分，称为功能性肝脏氮清除率（FHNC）。八名男性志愿者在三个不同时段接受随机研究：1）静脉输注生理盐水12小时后；2）静脉输注GH（1 IU/小时）12小时后；3）皮下注射GH（8 IU/天）2天后，接着静脉输注GH（1 IU/小时）12小时后。在接受GH治疗期间，丙氨酸输注时的UNSR（毫摩尔/小时）显著降低[最大值±标准误，133.0±6.9（生理盐水）对96.7±11.1（12小时GH；P<0.01）对106.5±7.5（2天GH；P<0.05）]。三项研究中的FHNC（升/小时）相似[30.3±1.2（生理盐水）对26.6±3.4（12小时GH）对27.0±2.6（2天GH）]。六名生长激素缺乏的成年患者接受两次随机研究：1）每日常规（2000时）皮下注射GH治疗（3 IU/m²·天）后；2）停用GH 2天后。患者接受GH治疗时，丙氨酸输注期间的UNSR同样显著降低[147.7±11.7 mmol/小时（未用GH）对123.9±9.1 mmol/小时；P<0.01]。两项研究中的FHNC（升/小时）值相似[29.2±3.8（GH）对27.5±4.5（未用GH）]。我们的数据证实了GH的合成代谢作用，并表明短期缺乏GH与分解代谢相关，表现为UNSR增加。FHNC未改变这一发现提示GH诱导的肝外氨基氮转化调节，而非不依赖底物的肝脏机制。
