Mouse models of growth hormone action and aging: a proteomic perspective

Abstract

Growth hormone (GH) is a protein secreted by the anterior pituitary and circulates throughout the body to exert important actions on growth and metabolism. GH stimulates the secretion of insulin-like growth factor-I (IGF-I) that mediates some of the growth promoting actions of GH. The GH/IGF-I axis has recently been recognized as important in terms of longevity in organisms ranging from Caenorhabditis elegans to mice. For example, GH transgenic mice possess short lifespans while GH receptor null (GHR-/-) mice have extended longevity. Thus, the actions of GH (or IGF-I) or lack thereof impact the aging process. In this review, we summarize the proteomic analyses of plasma and white adipose tissue in these two mouse models of GH action, i.e. GH transgenic and GHR-/- mice. At the protein level, we wanted to establish novel plasma biomarkers of GH action as a function of age and to determine differences in adipose tissue depots. We have shown that these proteomic approaches have not only confirmed several known physiological actions of GH, but also resulted in novel protein biomarkers and targets that may be indicative of the aging process and/or new functions of GH. These results may generate new directions for GH and/or aging research.

Figure 1

A schematic flow chart of protein isolation by 2-DE, then identification by MS and MS/MS. 2-DE: two-dimensional electrophoresis, MS: mass spectrometry, PMF: peptide mass fingerprint, R: arginine; K: lysine. This figure was adapted from that found on the Michigan Proteome Consortium web page.

Figure 2

2-DE gel map of mouse plasma proteome with annotations of proteins that are significantly different in bGH and/or GHR−/− mice. Mw = molecular weight; pI = isoelectric point; A2M = alpha-2 macroglobulin; APOA4 = apolipoprotein A-4; APOA1 = apolipoprotein A-1; APOE = apolipoprotein E; CLU= clusterin; HP = haptoglobin; MBP-C = mannose-binding protein-C; RBP-4 = retinol-binding protein-4; TTR = transthyretin.

Figure 3

2-DE gel map of mouse white adipose tissue with annotations of proteins that are significantly different between GHR−/− mice and wild-type littermates (P<0.01). Main effects are labeled using (○) for genotype; (□) for depot; and (x) for age. Significant interactions are labeled with capital letters: genotype × depot (A); genotype × age (B); depot × age (C); and genotype × depot × age (D). Dashed circles mark spots that only show significant interaction effects. The identities of certain spots are annotated; αFP = α fetoprotein; APOA1 = apolipoprotein A-1; ATP5H = ATP synthase subunit β, mitochondrial; CA-III = carbonic anhydrase 3; CKB = creatine kinase B; E-FABP = Fatty acid-binding protein, epidermal; ERp29 = Endoplasmic reticulum resident protein 29; Idh3α = isocitrate dehydrogenase [NAD+] α; MYL9 = myosin regulatory light polypeptide 9; PDHE-B = Pyruvate dehydrogenase E1 β, mitochondrial; PPIase = Peptidyl-prolyl cis-trans isomerase A; SOD1 = superoxide dismutase [Cu–Zn]; TIM = triosephosphate isomerase; TTR = transthyretin.