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迈向生长激素(GH)滥用检测方法的开发:对813名精英运动员赛后生长激素依赖标志物极端生理范围的研究

Toward the development of a test for growth hormone (GH) abuse: a study of extreme physiological ranges of GH-dependent markers in 813 elite athletes in the postcompetition setting.

作者信息

Healy Marie-Louise, Dall Rolf, Gibney James, Bassett Eryl, Ehrnborg Christer, Pentecost Claire, Rosen Thord, Cittadini Antonio, Baxter Robert C, Sönksen Peter H

机构信息

Department of Diabetes and Endocrinology, GKT School of Medicine, St. Thomas' Hospital, London, UK.

出版信息

J Clin Endocrinol Metab. 2005 Feb;90(2):641-9. doi: 10.1210/jc.2004-0386. Epub 2004 Nov 16.

Abstract

There is a need to develop a test to detect GH abuse by elite athletes. Measured levels of GH in blood or urine, however, provide little information on the GH-IGF-I axis. Previous studies have identified a series of indirect markers of GH action that are markedly altered by the administration of GH, but to a lesser degree by acute exercise. This study was undertaken to determine the physiological range of these GH-dependent variables in elite athletes after a competitive event to determine whether such values differ from resting values in normal and athletic subjects and to establish whether any adjustments to this range are required on the basis of age, gender, demographic characteristics, or the nature of the exercise performed. Serum samples were collected from 813 elite athletes (537 males and 276 females; age range, 17-64 yr) from 15 sporting disciplines within 2 h of completion of a major competitive event. IGF-I, IGF-binding protein 2 (IGFBP-2), IGFBP-3, acid-labile subunit, and the bone and soft tissue markers, osteocalcin, carboxyl-terminal propeptide of type I procollagen, carboxyl-terminal cross-linked telopeptide of type I collagen, and procollagen type III were measured. Sporting category, gender, age, height, weight, body mass index (BMI), and racial group of the athlete were documented, and results were compared both to normative data and to values obtained from elite athletes under resting conditions. Forty-one percent of IGF-I values in male athletes and 41% of values in female athletes were above the upper limits of 99% reference ranges derived from resting values in a normal population. Postcompetition levels of all variables except carboxyl-terminal propeptide of type I procollagen and carboxyl-terminal cross-linked telopeptide of type I collagen differed from resting values. There was a consistent age-dependent fall in measured levels of all variables (P < 0.0001) with the exception of IGFBP-2, which increased with age (P < 0.0001). BMI, but not height, exerted a small, but significant, influence on several variables. After adjustment for age, there were no significant differences in the levels of any of the measured variables between sporting categories. IGFBP-2 and IGFBP-3 were lower in 35 black athletes compared with those in 35 white athletes matched for age, gender, height, BMI, and sporting category. We have demonstrated that there are predictable age-dependent levels of GH-dependent markers in elite athletes that are consistent even at the extremes of physical exertion and that these are independent of sporting category. Normative data applicable to white athletes are provided. This provides important groundwork for the development of a test for GH abuse, although these values may be specific for the reagents and assays used.

摘要

有必要开发一种检测精英运动员生长激素滥用情况的测试方法。然而,血液或尿液中生长激素的测量水平几乎无法提供有关生长激素-胰岛素样生长因子-I轴的信息。先前的研究已经确定了一系列生长激素作用的间接标志物,这些标志物在使用生长激素后会发生显著变化,但在急性运动时变化程度较小。本研究旨在确定精英运动员在一项竞技赛事后这些生长激素依赖变量的生理范围,以确定这些值与正常和运动员受试者的静息值是否不同,并确定是否需要根据年龄、性别、人口统计学特征或所进行运动的性质对该范围进行任何调整。在一项重大竞技赛事结束后2小时内,从15个运动项目的813名精英运动员(537名男性和276名女性;年龄范围17 - 64岁)中采集血清样本。测量了胰岛素样生长因子-I(IGF-I)、胰岛素样生长因子结合蛋白2(IGFBP-2)、IGFBP-3、酸不稳定亚基以及骨和软组织标志物骨钙素、I型前胶原羧基末端前肽、I型胶原羧基末端交联端肽和III型前胶原。记录了运动员的运动类别、性别、年龄、身高、体重、体重指数(BMI)和种族,并将结果与标准数据以及在静息条件下从精英运动员获得的值进行比较。男性运动员中41%的IGF-I值和女性运动员中41%的值高于从正常人群静息值得出的99%参考范围的上限。除I型前胶原羧基末端前肽和I型胶原羧基末端交联端肽外,所有变量的赛后水平均与静息值不同。除IGFBP-2随年龄增加(P < 0.0001)外,所有变量的测量水平均随年龄持续下降(P < 0.0001)。BMI对几个变量有微小但显著的影响,而身高没有。在对年龄进行调整后,不同运动类别之间任何测量变量的水平均无显著差异。35名黑人运动员的IGFBP-2和IGFBP-3低于35名年龄、性别、身高、BMI和运动类别相匹配的白人运动员。我们已经证明,精英运动员中存在可预测的、与年龄相关的生长激素依赖标志物水平,即使在极度体力消耗时也是一致的,并且这些与运动类别无关。提供了适用于白人运动员的标准数据。这为开发生长激素滥用测试提供了重要的基础工作,尽管这些值可能特定于所使用的试剂和检测方法。

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