Grøfte T, Jensen D S, Grønbaek H, Wolthers T, Jensen S A, Tygstrup N, Vilstrup H
Department of Medicine V, Aarhus University Hospital, DK-8000 Aarhus C, Denmark.
Am J Physiol. 1998 Jul;275(1):E79-86. doi: 10.1152/ajpendo.1998.275.1.E79.
Growth hormone (GH) reduces the catabolic side effects of steroid treatment due to its effects on tissue protein synthesis/degradation. Little attention is focused on hepatic amino acid degradation and urea synthesis. Five groups of rats were given 1) placebo, 2) prednisolone, 3) placebo, pair fed to the steroid group, 4) GH, and 5) prednisolone and GH. After 7 days, the in vivo capacity of urea N synthesis (CUNS) was determined by saturating alanine infusion, in parallel with measurements of liver mRNA levels of urea cycle enzymes, N contents of organs, N balance, and hormones. Prednisolone increased CUNS (micromol . min-1 . 100 g-1, mean +/- SE) from 9.1 +/- 1.0 (pair-fed controls) to 13.2 +/- 0.8 (P < 0.05), decreased basal blood alpha-amino N concentration from 4.2 +/- 0.5 to 3.1 +/- 0.3 mmol/l (P < 0.05), increased mRNA levels of the rate- and flux-limiting urea cycle enzymes by 20 and 65%, respectively (P < 0. 05), and decreased muscle N contents and N balance. In contrast, GH decreased CUNS from 6.1 +/- 0.9 (free-fed controls) to 4.2 +/- 0.5 (P < 0.05), decreased basal blood alpha-amino N concentration from 3. 8 +/- 0.3 to 3.2 +/- 0.2, decreased mRNA levels of the rate- and flux-limiting urea cycle enzymes to 60 and 40%, respectively (P < 0. 05), and increased organ N contents and N balance. Coadministration of GH abolished all steroid effects. We found that prednisolone increases the ability of amino N conversion into urea N and urea cycle gene expression. GH had the opposite effects and counteracted the N-wasting side effects of prednisolone.
生长激素（GH）因其对组织蛋白质合成/降解的作用，可减轻类固醇治疗的分解代谢副作用。人们很少关注肝脏氨基酸降解和尿素合成。将大鼠分为五组，分别给予：1）安慰剂；2）泼尼松龙；3）与类固醇组配对喂食的安慰剂；4）生长激素；5）泼尼松龙和生长激素。7天后，通过饱和丙氨酸输注测定尿素氮合成的体内能力（CUNS），同时测量尿素循环酶的肝脏mRNA水平、器官氮含量、氮平衡和激素水平。泼尼松龙使CUNS（微摩尔·分钟-1·100克-1，平均值±标准误）从9.1±1.0（配对喂食对照组）增加到13.2±0.8（P<0.05），使基础血α-氨基氮浓度从4.2±0.5降至3.1±0.3毫摩尔/升（P<0.05），使限速和通量限制尿素循环酶的mRNA水平分别增加20%和65%（P<0.05），并降低肌肉氮含量和氮平衡。相比之下，生长激素使CUNS从6.1±0.9（自由喂食对照组）降至4.2±0.5（P<0.05），使基础血α-氨基氮浓度从3.8±0.3降至3.2±0.2，使限速和通量限制尿素循环酶的mRNA水平分别降至60%和40%（P<0.05），并增加器官氮含量和氮平衡。生长激素与泼尼松龙联合使用消除了所有类固醇效应。我们发现，泼尼松龙增加了氨基氮转化为尿素氮的能力和尿素循环基因表达。生长激素则具有相反的作用，并抵消了泼尼松龙的氮消耗副作用。
