Proteomic profiling of growth hormone-responsive proteins in human peripheral blood leukocytes.

Author(s): Chung L, Nelson AE, Ho KK, Baxter RC

Affiliation(s): Kolling Institute of Medical Research, University of Sydney, Royal North Shore Hospital, St. Leonards 2065, Australia.

Publication date & source: 2009-08, J Clin Endocrinol Metab., 94(8):3038-43. Epub 2009 Jun 2.

Publication type: Randomized Controlled Trial; Research Support, Non-U.S. Gov't

CONTEXT: GH is a known modulator of the immune system, but the effect of exogenous GH administration on white blood cell proteins has not been investigated. Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) is a powerful platform for the study of GH effects on immune system proteins. OBJECTIVE: Our objective was to explore a novel approach for the detection of GH-responsive proteins in human leukocytes by proteomic analysis using SELDI-TOF MS. DESIGN: We conducted a randomized double-blind, placebo-controlled GH administration study of 8 wk treatment followed by 6 wk washout. Pre- and posttreatment samples from 30 subjects were used for biomarker discovery. SETTING: The study was performed at a clinical research facility. PARTICIPANTS: We studied 30 recreationally trained healthy athletes. INTERVENTION: Subjects received either recombinant human GH (2 mg/d sc; n = 22) or placebo (n = 8) for 8 wk. MAIN OUTCOME MEASURES: Proteomic profiles were determined using CM10 weak cation-exchange protein chips, and some GH-regulated proteins were purified and identified by mass spectrometry and/or immunoblotting. RESULTS: SELDI-TOF analysis revealed a number of GH-regulated peptides/proteins in the 3- to 22-kDa range that are either up- or down-regulated by GH. Several of these may be useful as biomarkers of GH action. The calcium-binding, proinflammatory calgranulins S100A8, S100A9, and S100A12 were all significantly down-regulated in response to GH treatment. CONCLUSION: This study illustrates the novel use of human leukocyte proteomic profiling by SELDI-TOF MS and reveals the negative regulation of proinflammatory S100 proteins by GH in human white blood cells.