Wolthers T, Grøfte T, Jørgensen J O, Vilstrup H
Department of Medicine M (Endocrinology and Diabetes), Aarhus University Hospital, Kommunehospitalet, Denmark.
J Hepatol. 1997 Nov;27(5):789-95. doi: 10.1016/s0168-8278(97)80314-5.
BACKGROUND/AIMS: Glucocorticoid treatment increases urea excretion and leads to negative nitrogen balance. This effect is presumed mainly to reflect actions on tissue protein metabolism, but has been shown in rats to involve an hepatic element in the form of upregulation of the kinetics of ureagenesis. Likewise, the anabolic action of growth hormone administration has been shown to involve an hepatic element, just as growth hormone administration has been shown to prevent the protein catabolic side effects of prednisolone. Whether glucocorticoids increase the ability of the liver to convert amino-N to urea-N in man, and whether growth hormone counteracts any possible effect of glucocorticoid has not been studied.
We measured urea nitrogen synthesis rates and blood alpha-amino-N levels before, during, and after a 4-h constant i.v. infusion of alanine (2 mmol x kg BW(-1) x h(-1)). The urea nitrogen synthesis rate was estimated hourly as urinary excretion corrected for gut hydrolysis and accumulation in body water. The slope of the linear relationship between urea nitrogen synthesis rate and amino-N concentration represents the hepatic kinetics of conversion of amino- to urea-N, and is denoted the functional hepatic nitrogen clearance. Eight normal male subjects (aged 22-28 years; BMI 21.6-26.3 kg/m2) were randomly studied four times: i) after 4 days of s.c. saline injections, ii) after 4 days of s.c. growth hormone injections (0.1 IU x kg(-1) x day(-1)), iii) after 4 days of glucocorticoid administration (50 mg/d) and iv) after 4 days of growth hormone and glucocorticoid administration. All injections were given at 20 00 hours and 25 mg prednisolone was given morning and evening.
Growth hormone decreased functional hepatic nitrogen clearance (l/h) by 21% (from 38.8+/-1.8 l/h (control) to 30.5+/-2.7 l/h (4 d growth hormone) (mean+/-SE) (ANOVA; p<0.05)). Glucocorticoid increased functional hepatic nitrogen clearance by 23% (47.7+/-3.3 l/h, p<0.05), while growth hormone plus glucocorticoid offset any effect on functional hepatic nitrogen clearance (36.2+/-3.3 l/h, p=0.83).
Glucocorticoid administration leads to loss of nitrogen as urea, in part due to a specific hepatic mechanism, as shown by the increased functional hepatic nitrogen clearance. Growth hormone has the opposite effect, and also neutralises the glucocorticoid effect when given together with prednisolone. This adds to the understanding of the development and treatment possibilities of steroid catabolism.
背景/目的：糖皮质激素治疗会增加尿素排泄并导致负氮平衡。这种效应主要被认为反映了对组织蛋白质代谢的作用，但在大鼠中已表明其涉及以尿素生成动力学上调形式存在的肝脏因素。同样，生长激素给药的合成代谢作用也已表明涉及肝脏因素，正如生长激素给药已被证明可预防泼尼松龙的蛋白质分解代谢副作用一样。糖皮质激素是否会增加人体肝脏将氨基氮转化为尿素氮的能力，以及生长激素是否会抵消糖皮质激素的任何可能作用，尚未得到研究。
我们在静脉内持续输注丙氨酸（2 mmol·kg体重⁻¹·h⁻¹）4小时之前、期间和之后，测量了尿素氮合成速率和血液α-氨基氮水平。尿素氮合成速率每小时通过校正肠道水解和体内水蓄积后的尿排泄量来估算。尿素氮合成速率与氨基氮浓度之间线性关系的斜率代表了氨基氮向尿素氮转化的肝脏动力学，被称为功能性肝脏氮清除率。八名正常男性受试者（年龄22 - 28岁；体重指数21.6 - 26.3 kg/m²）被随机进行了四次研究：i）皮下注射生理盐水4天后；ii）皮下注射生长激素（0.1 IU·kg⁻¹·天⁻¹）4天后；iii）给予糖皮质激素（50 mg/d）4天后；iv）给予生长激素和糖皮质激素4天后。所有注射均在20:00进行，且早晚各给予25 mg泼尼松龙。
生长激素使功能性肝脏氮清除率（升/小时）降低了21%（从38.8±1.8升/小时（对照）降至30.5±2.7升/小时（生长激素4天）（均值±标准误）（方差分析；p<0.05））。糖皮质激素使功能性肝脏氮清除率增加了23%（47.7±3.3升/小时，p<0.05），而生长激素加糖皮质激素抵消了对功能性肝脏氮清除率的任何影响（36.2±3.3升/小时，p = 0.83）。
给予糖皮质激素会导致氮以尿素形式流失，部分原因是一种特定的肝脏机制，这表现为功能性肝脏氮清除率增加。生长激素具有相反的作用，并且与泼尼松龙一起给药时也能抵消糖皮质激素的作用。这有助于加深对类固醇分解代谢的发展和治疗可能性的理解。
