Christ E R, Cummings M H, Jackson N, Stolinski M, Lumb P J, Wierzbicki A S, Sönksen P H, Russell-Jones D L, Umpleby A M
Department of Endocrinology and Diabetology, University Hospital of Bern, Bern CH-3100, Switzerland.
J Clin Endocrinol Metab. 2004 Apr;89(4):1801-7. doi: 10.1210/jc.2003-031474.
GH replacement therapy has been shown to improve the dyslipidemic condition in a substantial proportion of patients with adult GH deficiency. The mechanisms are not yet fully elucidated. Low-density lipoprotein (LDL) apolipoprotein B100 (apoB) formation and catabolism are important determinants of plasma cholesterol concentrations. This study examined the effect of GH replacement therapy on LDL apoB metabolism using a stable isotope turnover technique. LDL apoB kinetics was determined in 13 adult patients with GH deficiency before and after 3 months GH/placebo treatment in a randomized, double-blind, placebo-controlled study. LDL apoB (13)C-leucine enrichment was determined by isotope-ratio mass spectrometry. Plasma volume was assessed by standardized radionuclide dilution technique. GH replacement therapy significantly decreased LDL cholesterol, LDL apoB concentrations, and LDL apoB pool size compared with placebo. Compared with baseline, GH replacement therapy resulted in a significant increase in plasma volume and fractional catabolic rate, whereas LDL formation rate remained unchanged. LDL lipid content did not significantly change after GH and placebo. This study suggests that short-term GH replacement therapy decreases the LDL apoB pool by increasing removal of LDL particles without changing LDL composition or LDL apoB production rate. In addition, it is possible that the beneficial effects of GH on the cardiovascular system contribute to these findings.
生长激素替代疗法已被证明能改善相当一部分成年生长激素缺乏患者的血脂异常状况。其机制尚未完全阐明。低密度脂蛋白（LDL）载脂蛋白B100（apoB）的形成和分解代谢是血浆胆固醇浓度的重要决定因素。本研究使用稳定同位素周转技术研究了生长激素替代疗法对LDL apoB代谢的影响。在一项随机、双盲、安慰剂对照研究中，对13名成年生长激素缺乏患者在接受3个月生长激素/安慰剂治疗前后的LDL apoB动力学进行了测定。通过同位素比率质谱法测定LDL apoB（13）C-亮氨酸富集情况。采用标准化放射性核素稀释技术评估血浆容量。与安慰剂相比，生长激素替代疗法显著降低了LDL胆固醇、LDL apoB浓度和LDL apoB池大小。与基线相比，生长激素替代疗法导致血浆容量和分解代谢率显著增加，而LDL生成率保持不变。生长激素和安慰剂治疗后，LDL脂质含量无显著变化。本研究表明，短期生长激素替代疗法通过增加LDL颗粒的清除而不改变LDL组成或LDL apoB产生率来降低LDL apoB池。此外，生长激素对心血管系统的有益作用可能促成了这些发现。
