Growth hormone secretion pattern is an independent regulator of growth hormone actions in humans
Growth hormone secretion pattern is an independent regulator of growth hormone actions in humans
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DOI：
10.1152/ajpendo.00513.2001
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发表时间：
2002-11-01
影响因子：
5.1
通讯作者：
Watkins, PB
中科院分区：
文献类型：
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作者：
Jaffe, CA;Turgeon, DK;Watkins, PB
在啮齿动物中，性别特异性生长激素(GH)的分泌模式在调节生长和代谢方面的重要性已经被清楚地证明。我们最近发现，人类的生长激素分泌也是性二态的。生长激素的分泌模式是否调节生长激素在人体内的代谢作用在很大程度上尚不清楚。为了解决这个问题，我们每天静脉注射相同剂量的生长激素(0.5毫克·米(-2)·天(-1))，以不同的方式给9名生长激素缺乏的成年人连续8天。每个受试者被研究了四种情况：方案1(不治疗)，方案2(0100时80%每日剂量，0900和1700时10%每日剂量)，方案3(每3h 8次等量注射)，方案4(持续GH输注)。测定生长激素对血清IGF-I、IGF结合蛋白(IGFBP)-3、骨钙素和尿脱氧吡啶的影响。分别用咖啡因呼气试验和红霉素呼气试验测定肝脏细胞色素P450 1A2和细胞色素P3A4活性。方案3和方案4在提高血清IGF-I和IGFBP-3方面最有效，而应用搏动性生长激素方案对骨形成和骨吸收的标志物影响最大。所有生长激素处理都降低了细胞色素P1A2的活性，其中以搏动性生长激素的影响最大。搏动性GH降低，持续GH输注增加，细胞色素P3A4活性升高。这些数据表明，生长激素脉搏模式是人体生长激素作用的一个独立参数。药物代谢的性别差异，以及潜在的性别生长率差异，可以通过性别特定的生长激素分泌模式来解释。
The importance of gender-specific growth hormone (GH) secretion pattern in the regulation of growth and metabolism has been demonstrated clearly in rodents. We recently showed that GH secretion in humans is also sexually dimorphic. Whether GH secretion pattern regulates the metabolic effects of GH in humans is largely unknown. To address this question, we administered the same daily intravenous dose of GH (0.5 mg.m(-2).day(-1)) for 8 days in different patterns to nine GH-deficient adults. Each subject was studied on four occasions: protocol 1 (no treatment), protocol 2 (80% daily dose at 0100 and 10% daily dose at 0900 and 1700), protocol 3 (8 equal boluses every 3 h), and protocol 4 (continuous GH infusion). The effects of GH pattern on serum IGF-I, IGF-binding protein (IGFBP)-3, osteocalcin, and urine deoxypyridinoline were measured. Hepatic CYP1A2 and CYP3A4 activities were assessed by the caffeine and erythromycin breath tests, respectively. Protocols 3 and 4 were the most effective in increasing serum IGF-I and IGFBP-3, whereas protocols administering pulsatile GH had the greatest effects on markers of bone formation and resorption. All GH treatments decreased CYP1A2 activity, and the effect was greatest for pulsatile GH. Pulsatile GH decreased, whereas continuous GH infusion increased, CYP3A4 activity. These data demonstrate that GH pulse pattern is an independent parameter of GH action in humans. Gender differences in drug metabolism and, potentially, gender differences in growth rate may be explained by sex-specific GH secretion patterns.