Testosterone deficiency in young men: Marked alterations in whole body protein kinetics, strength, and adiposity
Testosterone deficiency in young men: Marked alterations in whole body protein kinetics, strength, and adiposity
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DOI：
10.1210/jc.83.6.1886
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发表时间：
1998-06-01
影响因子：
5.8
通讯作者：
Urban, RJ
中科院分区：
文献类型：
--
作者：
Mauras, N;Hayes, V;Urban, RJ
为了研究雄激素对全身代谢的具体影响，我研究了6名健康的瘦男性（平均+/- SEM年龄，23.2 +/- 0.5岁）在使用GnRH类似物（Lupron）进行性腺类固醇抑制之前和之后，给予两次，间隔3周。在基线（D1）和治疗10周后（D2）进行[C-13]亮氨酸预充输注、间接量热法、等速测力法、生长因子测量和经皮肌肉活检;每例受试者作为其自身对照。治疗10周后，睾酮浓度明显受到抑制（D1，535 +/- 141 ng/dL; D2，31 +/- 9）。在性腺功能减退10周后，亮氨酸的出现率（蛋白质水解）明显受到抑制（-13%，P = 0.01），以及非氧化性亮氨酸处理，全身蛋白质合成的指数（-13%，P = 0.01），血浆氨基酸浓度没有任何变化。10周后，所有受试者通过皮褶卡尺和双发射X射线荧光测量扫描显示，（D1，56.5 +/- 2.9 kg; D2，54.4 +/- 2.5; P = 0.005），以及脂肪质量百分比增加（D1，19.2 +/- 2.5%; D2，22.2 +/- 2.5; P = 0.001）。治疗后脂质氧化率降低（-31%; P = 0.05），静息能量消耗发生平行变化（-9%; P = 0.05）。平均和峰值GH浓度（每10分钟测量一次，持续6小时）和GH产生率在睾酮缺乏后没有降低，实际上基础分泌增加（P < 0.02）。治疗10周后，血浆胰岛素样生长因子I（IGF-I）浓度未发生显著变化（D1，227 +/- 44 μ g/L; D2，291 +/- 60; P = 0.08）。60度和180度/s的腿部伸肌等速肌力在性腺功能减退10周后也降低。从肌肉活检样本中分离总核糖核酸（RNA），并使用IGF-1、IGF结合蛋白-4、肌球蛋白和肌动蛋白的人互补DNA克隆进行核糖核酸酶保护试验。Lupron治疗10周后，IGF-I的信使RNA（mRNA）浓度显著降低，而IGF-结合蛋白-4浓度有升高的趋势，肌球蛋白或肌动蛋白mRNA浓度无变化。总之，年轻男性睾酮缺乏与全身蛋白含量显著降低、力量下降、脂肪氧化减少和肥胖增加有关。睾酮缺乏的这些影响是独立的外周GH的生产和IGF-I浓度的变化，即使IM IGF-I mRNA浓度降低。这些数据表明雄激素对全身脂质和蛋白质代谢的直接影响。
To investigate specific effects of androgens on whole body metabolism, me studied six healthy lean men (mean +/- SEM age, 23.2 +/- 0.5 yr) before and after gonadal steroid suppression with a GnRH analog (Lupron), given twice, 3 weeks apart. Primed infusions of [C-13]leucine, indirect calorimetry, isokinetic dynamometry, growth factor measurements, and percutaneous muscle biopsies were performed at baseline (D1) and after 10 weeks of treatment (D2); each subject served as his own control. Testosterone concentrations were markedly suppressed after 10 weeks of treatment (D1, 535 +/- 141 ng/dL; D2, 31 +/- 9). Leucine's rate of appearance tinder of proteolysis) was markedly suppressed after 10 weeks of hypogonadism (-13%; P = 0.01) as well as the nonoxidative leucine disposal, an index of whole body protein synthesis (-13%; P = 0.01) without any changes in plasma amino acid concentrations. All subjects studied after 10 weeks showed a decrease in fat-free mass, as measured by skinfold calipers and dual emission x-ray absortiometry scans (D1, 56.5 +/- 2.9 kg; D2, 54.4 +/- 2.5; P = 0.005), and an increase in percent fat mass (D1, 19.2 +/- 2.5%; D2, 22.2 +/- 2.5; P = 0.001). Rates of lipid oxidation decreased (-31%; P = 0.05) after treatment, with parallel changes in resting energy expenditure (-9%; P = 0.05). Mean and peak GH concentrations (measured every 10 min for 6 h) and GH production rates did not decrease after testosterone deficiency, with an actual increase in basal secretion (P < 0.02). Plasma insulin-like growth factor I(IGF-I) concentrations did not change significantly after 10 weeks of treatment (D1, 227 +/- 44 mu g/L; D2, 291 +/- 60; P = 0.08). Isokinetic dynamometry of leg extensors at 60 degrees and 180 degrees/s was also decreased after 10 weeks of hypogonadism. Total ribonucleic acid (RNA) was isolated from muscle biopsy samples, and ribonuclease protection assays were performed using human complementary DNA clones for IGF-I, IGF-binding protein-4, myosin, and actin. Ten weeks after Lupron treatment, messenger RNA (mRNA) concentrations of IGF-I decreased significantly, whereas there was a trend toward higher IGF-binding protein-4 concentrations, with no change in myosin or actin mRNA concentrations.In conclusion, testosterone deficiency in young men is associated with a marked decrease in measures of whole body protein anabolism, decreased strength, decreased fat oxidation, and increased adiposity. These effects of testosterone deficiency are independent of changes in peripheral GH production and IGF-I concentrations, even though im IGF-I mRNA concentrations decrease. These data suggest a direct effect of androgens on whole body lipid and protein metabolism.