The impact of growth hormone on proteomic profiles: a review of mouse and adult human studies

Abstract

Growth hormone (GH) is a protein that is known to stimulate postnatal growth, counter regulate insulin’s action and induce expression of insulin-like growth factor-1. GH exerts anabolic or catabolic effects depending upon on the targeted tissue. For instance, GH increases skeletal muscle and decreases adipose tissue mass. Our laboratory has spent the past two decades studying these effects, including the effects of GH excess and depletion, on the proteome of several mouse and human tissues. This review first discusses proteomic techniques that are commonly used for these types of studies. We then examine the proteomic differences found in mice with excess circulating GH (bGH mice) or mice with disruption of the GH receptor gene (GHR−/−). We also describe the effects of increased and decreased GH action on the proteome of adult patients with either acromegaly, GH deficiency or patients after short-term GH treatment. Finally, we explain how these proteomic studies resulted in the discovery of potential biomarkers for GH action, particularly those related with the effects of GH on aging, glucose metabolism and body composition.Electronic supplementary materialThe online version of this article (doi:10.1186/s12014-017-9160-2) contains supplementary material, which is available to authorized users.

Annual banned‐substance review: Analytical approaches in human sports drug testing

“…Underlying hGH‐induced mechanisms potentially enhancing athletic performance have been the subject of intense debate and the relevance of other (prohibited) substances co‐administered with hGH has been discussed frequently . The quantification and (longitudinal) profiling of hGH isoforms and/or biomarkers identified in proteomics studies has become a mainstay in detecting hGH misuse, and the possibility of determining hGH isoforms and biomarkers in dried blood spots (DBS) has been recently presented. The option of using DBS for monitoring growth hormone isoforms as commonly conducted with doping control serum samples was assessed by Reverter‐Branchat et al In a clinical trial, 8 male volunteers received subcutaneous injections of hGH at 0.027 mg/kg/day for 3 consecutive days, and DBS as well as serum and plasma were collected up to 72 hours post‐administration.…”

A role for metabolomics in the antidoping toolbox?

“…Genomics, transcriptomics, proteomics, and metabolomics have proven to be suitable for the detection of the whole set of genes, transcripts, proteins, or metabolites (respectively), in a precise and repeatable manner. Genomics and transcriptomics have already been proposed as screening strategies for gene doping, 31,35 while proteomics has been proposed as a screening tool for hormone doping 36–40 . Metabolomics has proven to be a highly suitable tool for studying the metabolism of living matter, including humans 41 .…”

Differential gene signature in adipose tissue depots of growth hormone transgenic mice

“…1 The giant bovine GH (bGH) transgenic mice share many features with the clinical condition of acromegaly and have been extensively studied to evaluate the effects of excess GH action in vivo. [2][3][4][5] Similar to acromegaly, bGH mice have elevated serum GH and IGF-1 levels, 4,5 although individuals with acromegaly exhibit high basal, yet pulsatile GH serum levels, 6,7 whereas bGH mice have a life-long, continuous serum GH elevation. GH has an anabolic effect on muscle and a catabolic effect on adipose tissue (AT).…”

“…That is, adult bGH mice exhibit insulin resistance and hyperinsulinaemia, even though body composition is favorable with dramatically reduced fat mass and increased lean mass. 2,3,7 Patients with acromegaly and bGH mice both exhibit increased incidence of cancer, 8 cardiovascular 9-11 and kidney diseases, [12][13][14] as well as a significantly decreased lifespan, compared to controls with normal GH action. 3,15,16 AT, a highly dynamic organ, has drawn attention in the quest to understand how GH impacts health and longevity.…”

“…Acromegaly is an acquired condition characterised by increased circulating growth hormone (GH) and insulin‐like growth factor (IGF)‐1 levels and profound metabolic complications that ultimately lead to premature death 1 . The giant bovine GH (bGH) transgenic mice share many features with the clinical condition of acromegaly and have been extensively studied to evaluate the effects of excess GH action in vivo 2‐5 . Similar to acromegaly, bGH mice have elevated serum GH and IGF‐1 levels, 4,5 although individuals with acromegaly exhibit high basal, yet pulsatile GH serum levels, 6,7 whereas bGH mice have a life‐long, continuous serum GH elevation.…”