Laursen T, Møller J, Jørgensen J O, Orskov H, Christiansen J S
Medical Department M (Diabetes and Endocrinology), Aarhus University Hospital, Denmark.
Clin Endocrinol (Oxf). 1996 Sep;45(3):333-9. doi: 10.1046/j.1365-2265.1996.00814.x.
The bioavailability of GH immunoreactive serum concentrations is reduced following subcutaneous (s.c.) as compared with intravenous (i.v.) administration. Whether this difference also translates into a different biological activity remains to be investigated. The aim of the present study was to evaluate the short-term metabolic effects of GH following i.v. and s.c. delivery.
In a cross-over design 10 GH-deficient patients were randomized to receive GH (0.03 microgram (0.1 mU/kg/min) as a continuous i.v. or s.c. infusion for 39 hours on two different occasions. Preceding each study GH therapy was discontinued for 5 days. Serum profiles of GH, IGF-I, IGF-II, IGF binding protein 3 (IGFBP-3), insulin, glucose and non-esterified fatty acids (NEFA) were recorded during the studies. Serum GH was measured by a polyclonal radio-immunoassay (RIA) and by a double monoclonal immunofluorimetric assay (DELFIA).
Higher mean integrated values (AUC) of serum GH (mU/l) were obtained with i.v. GH delivery [47.4 +/- 5.1 (i.v.), 33.3 +/- 3.0 (s.c.), P < 0.05]. The two GH assays showed qualitatively similar results, but higher mean GH concentrations were measured by RIA following both s.c. (P < 0.001) and i.v. infusion (P < 0.001). Serum IGF-I levels displayed different patterns following i.v. and s.c. GH infusion (P < 0.05 by ANOVA) and mean IGF-I levels (micrograms/l) were lower following s.c. GH infusion [159.5 +/- 21.8 (s.c.), 185.2 +/- 27.7 (i.v.), P = 0.002]. Serum IGF-II levels were unaffected by short-term GH treatment and by the route of GH administration. Serum IGFBP-3 levels increased in response to GH administration (P < 0.001), irrespective of route (P = 0.76). The IGF-I/IGFBP-3 molar ratio increased significantly following GH administration (P < 0.001), and a higher ratio was obtained following i.v. infusion (P < 0.005). Subcutaneous GH infusion resulted in significantly lower mean levels of serum NEFA (P < 0.02), whereas similar mean levels of serum insulin (P = 0.54), blood glucose (P = 0.24), energy expenditure (P = 0.13), and respiratory exchange ratio (P = 0.09) were observed on the two occasions.
A reduced bioavailability of s.c. as compared with i.v. administered GH has been recorded with two independent GH assays, and this was also accompanied by a significant, albeit modest, reduction in biological activity.
与静脉注射（i.v.）相比，皮下注射（s.c.）生长激素（GH）后，血清中具有免疫反应性的GH浓度的生物利用度降低。这种差异是否也转化为不同的生物活性仍有待研究。本研究的目的是评估静脉注射和皮下注射GH后的短期代谢效应。
采用交叉设计，10例生长激素缺乏患者被随机分为两组，在两个不同时间段接受GH（0.03微克（0.1 mU/kg/min）持续静脉或皮下输注39小时。每次研究前，GH治疗中断5天。在研究过程中记录GH、胰岛素样生长因子-I（IGF-I）、胰岛素样生长因子-II（IGF-II）、胰岛素样生长因子结合蛋白3（IGFBP-3）、胰岛素、葡萄糖和非酯化脂肪酸（NEFA）的血清水平。血清GH通过多克隆放射免疫分析（RIA）和双单克隆免疫荧光分析（DELFIA）进行测量。
静脉注射GH时血清GH（mU/l）的平均积分值（AUC）更高[47.4±5.1（静脉注射），33.3±3.0（皮下注射），P<0.05]。两种GH检测方法显示出定性相似的结果，但皮下注射（P<0.001）和静脉输注（P<0.001）后，RIA检测的平均GH浓度更高。静脉注射和皮下注射GH后，血清IGF-I水平呈现不同模式（方差分析P<0.05），皮下注射GH后平均IGF-I水平（微克/升）较低[159.5±21.8（皮下注射），185.2±27.7（静脉注射），P = 0.002]。血清IGF-II水平不受短期GH治疗和GH给药途径的影响。血清IGFBP-3水平对GH给药有反应而升高（P<0.001），与给药途径无关（P = 0.76）。GH给药后IGF-I/IGFBP-3摩尔比显著升高（P<0.001），静脉输注后该比值更高（P<0.005）。皮下注射GH导致血清NEFA平均水平显著降低（P<0.02），而两次检测时血清胰岛素（P = 0.54）、血糖（P = 0.24）、能量消耗（P = 0.13）和呼吸交换率（P = 0.09）的平均水平相似。
两种独立的GH检测方法均记录到皮下注射GH与静脉注射相比生物利用度降低，并且这也伴随着生物活性显著但适度的降低。
