Novel biomarkers of human growth hormone action from serum proteomic profiling using protein chip mass spectrometry

J Clin Endocrinol Metab. 2006 Feb;91(2):671-7. doi: 10.1210/jc.2005-1137. Epub 2005 Nov 22.

Abstract

Context: The detection of exogenous human GH (hGH) administration in athletes poses unique analytical problems, because its short circulating half-life provides only a brief opportunity to detect the administered hormone above endogenous levels. Measurement of novel GH-regulated serum protein biomarkers might provide an indirect method to detect exogenous GH.

Objective: The objective of this study was to identify new serum biomarkers of GH administration using proteomic profiling.

Design: Sera from a previously reported, double-blind, placebo-controlled GH administration trial were analyzed by protein chip mass spectrometry.

Setting: The study was performed at clinical research centers.

Subjects: Sixty healthy subjects, aged 18-40 yr, who were not elite athletes, were studied.

Interventions: Placebo or recombinant hGH treatment (0.1 or 0.2 IU/kg.d; 20 subjects/group) was administered for 4 wk, followed by an 8-wk washout period.

Main outcome measures: Protein mass profiles were determined on immobilized Cu(2+) chips on d 0 and 21 of GH administration, and multivariate analysis was used to classify subjects into GH and placebo administration groups.

Results: When assessed by cross-validation, the classification performance of classifiers based on multivariate analysis of several GH-regulated peaks performed no better than classifiers based on the single best peak. This peak, a prominent biomarker of 15.1 kDa, was purified and identified as hemoglobin alpha-chain. The time course of the GH response of this biomarker is similar to that of other GH-dependent markers, such as IGF-I.

Conclusion: This study demonstrates that protein mass profiling is an effective tool for the detection of GH administration and suggests that measurement of hemoglobin alpha-chain may have utility as a novel serum biomarker of GH action.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers / blood
  • Double-Blind Method
  • Female
  • Glycated Hemoglobin A / analysis
  • Human Growth Hormone / blood*
  • Human Growth Hormone / pharmacology
  • Humans
  • Male
  • Mass Spectrometry / methods
  • Multivariate Analysis
  • Protein Array Analysis / methods
  • Proteomics / methods*
  • ROC Curve

Substances

  • Biomarkers
  • Glycated Hemoglobin A
  • Human Growth Hormone