| The growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis is an important regulator of longitudinal growth, metabolism and aging. The physiological role of GH is manifested in mouse models with altered GH signaling. For example, bovine (b) GH transgenic mice are giant, lean, insulin resistant and short-lived. In contrast, GH receptor (R) gene knockout (GHR-/-) mice are dwarf, obese, insulin sensitive and long-lived. In order to uncover the biomarkers of GH and aging, two-dimensional gel electrophoresis (2-DE) has been used to analyze the mouse plasma proteome. The bGH, GHR-/- mice and their respective controls at different ages were analyzed. Female GHR-/- and control mice were also analyzed for gender differences.;Several biomarkers of aging and GH actions have been discovered. Biomarkers for aging include proteins whose plasma levels increased (isoform(s) of transthyretin (TTR), haptoglobin (Hp), immunoglobulin kappa chain) and decreased (isoform(s) of albumin, serum amyloid A-1 (SAA-1) and peroxiredoxin-2). Biomarkers for chronic GH action include upregulation of apolipoprotein (apo) E, Hp, mannose-binding protein-C, specific isoform(s) of alpha-2 macroglobin (a2m), retinol-binding protein-4 (RBP-4), and downregulation of apoA4, TTR, specific isoforms of apoA1, a2m and RBP-4. Importantly, isoforms of Hp and clusterin increased markedly in bGH mice during aging compared to wild type (WT) mice, possibly indicating an accelerated aging phenotype of these mice. Gender-specific biomarkers include plasma proteins that increased such as isoform(s) of apoE and RBP-4 or decreased such as isoform(s) of clusterin, albumin, Hp and hemoblogin-beta in females. Interestingly, some proteins showed no change during male aging but significant increase (isoform(s) of apoA1, apoA4, TTR and albumin) or decrease (isoform(s) of RBP-4 and albumin) during female aging. In addition, several proteins (Hp, apoE and RBP-4) showed an interaction between genotype (GHR-/- and WT) and gender, suggesting interplay between GH and sex.;Finally, short-term effects of GH/IGF-1 were studied in mice injected with GH and/or IGF-1. GH injection resulted in upregulation of isoform(s) of apoE, Hp, RBP-4, SAA-1, albumin and a2m; and downregulated isoform(s) of apoA4 and clusterin. For IGF-1, isoform(s) of Hp, albumin and TTR were upregulated. Further, biomarkers differentiating between GH and IGF-1 actions have been revealed, including isoform(s) of apoE and TTR. The biomarkers of GH/IGF-1 injection will provide potential candidates for detecting GH and IGF-1 doping. |
