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


METHODS
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.


METHODS
The study was performed at a clinical research facility.


METHODS
We studied 30 recreationally trained healthy athletes.


METHODS
Subjects received either recombinant human GH (2 mg/d sc; n = 22) or placebo (n = 8) for 8 wk.


METHODS
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.


CONCLUSIONS
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.
Chung
Liping
L
Kolling Institute of Medical Research, University of Sydney, Royal North Shore Hospital, St. Leonards 2065, Australia.
Nelson
Anne E
AE
Ho
Ken K Y
KK
Baxter
Robert C
RC
D001798:Blood Proteins / Q000032:analysis*; D004311:Double-Blind Method; D005260:Female; D019382:Human Growth Hormone / Q000494:pharmacology*; D006801:Humans; D007962:Leukocytes / Q000737:chemistry*; D008297:Male; D040901:Proteomics / Q000379:methods*; D009418:S100 Proteins / Q000097:blood; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*
D001798:Blood Proteins; D009418:S100 Proteins; D019382:Human Growth Hormone