Activation of the GH/IGF-1 axis by CJC-1295, a long-acting GHRH analog, results in serum protein profile changes in normal adult subjects.
OBJECTIVE
To identify biomarkers of growth hormone (GH) and insulin-like growth factor 1 (IGF-1) action in human serum.


BACKGROUND
The search for new markers of GH activity has received extensive attention given that the current biomarkers (IGF-1, IGFBP-3 and collagen peptides) show substantial variability in the population, and are not reliably predictive of either the physiologic effects of GH therapy or the detection of GH abuse by athletes. GH releasing hormone (GHRH) is a polypeptide synthesized in the hypothalamus that binds to receptors on pituitary somatotropes to promote the synthesis and release of GH. Serum GH and IGF-1 levels have been shown to increase with administration of GHRH or CJC-1295, a long-acting GHRH analog.


METHODS
Sera from 11 healthy young adult men before and one week after CJC-1295 injection were analyzed by two-dimensional gel electrophoresis for proteomic changes. Serum proteins displaying significant changes before and after treatment were subsequently identified using mass spectrometry. In addition, correlations between these proteins and GH or IGF-1 levels were evaluated.


RESULTS
Two protein spots that displayed decreased intensities after treatment were identified as an apolipoprotein A1 isoform and a transthyretin isoform. Three protein spots upregulated by CJC-1295 treatment included beta-hemoglobin, a C-terminal fragment of albumin, and a mix of an immunoglobulin fragment and another C-terminal albumin fragment. A linear relationship was found between the spot containing immunoglobulin and albumin fragments and IGF-1 levels.


CONCLUSIONS
Although the molecular mechanisms linking the identified proteins to GH and IGF-1 biological activity remain to be clarified, the results suggest that they represent potential biomarkers of GH and/or IGF-1 action.
Sackmann-Sala
Lucila
L
Department of Biological Sciences, Ohio University, Athens, Ohio 45701, United States.
Ding
Juan
J
Frohman
Lawrence A
LA
Kopchick
John J
JJ
D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D001798:Blood Proteins / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods; D013006:Growth Hormone / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D008954:Models, Biological; D010446:Peptide Fragments / Q000494:pharmacology*; D010902:Pituitary Gland / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D011994:Recombinant Proteins / Q000737:chemistry
D015415:Biomarkers; D001798:Blood Proteins; C502076:CJC 1295; D010446:Peptide Fragments; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone