The Effect of Growth Hormone Administration on the Regulation of Mitochondrial Apoptosis in-Vivo.

James Keane,Bon Gray,Lotti Tajouri

doi:10.3390/ijms160612753

Abstract

The purpose of this study was to determine whether recombinant human growth hormone (rhGH) would show any significant effects on the expression of apoptosis regulating proteins in peripheral blood mononuclear cells (PBMCs). Additionally, the potential for post-transcriptional regulation of gene expression by miRNA was assessed in two cellular compartments, the cytosol and the mitochondria. Ten male subjects were subcutaneously injected with either rhGH (1 mg) or saline (0.9%) for seven consecutive days in a double-blinded fashion. Blood sampling was undertaken prior to treatment administration and over a period of three weeks following treatment cessation. Bcl-2 and Bak gene and protein expression levels were measured in PBMCs, while attention was also directed to the expression of miR-181a and miR-125b, known translational inhibitors of Bcl-2 and Bak respectively. Results showed that rhGH significantly decreased Bak protein concentrations compared to placebo samples for up to 8 days post treatment. While cytosolic miRNA expression was not found to be significantly affected by rhGH, measurement of the expression of miR-125b in mitochondrial fractions showed a significant down-regulation eight days post-rhGH administration. These findings suggest that rhGH induces short-term anti-apoptotic effects which may be partially mediated through a novel pathway that alters the concentration of mitochondrially-associated miRNAs.

Highlights

Apoptosis or “programmed cell death” is a physiologically favourable form of cell death which in addition to maintaining homeostatic control over cell populations, functions to remove damaged or diseased cells without incurring an inflammatory reaction [1,2]
The purpose of this study is to determine the effects on the regulation and expression of pro- and anti-apoptotic Bcl-2 family proteins in peripheral blood mononuclear cells (PBMCs) following the cessation of a seven day programme of recombinant human growth hormone (rhGH) administration in healthy trained male subjects for a period of three weeks
Bak protein concentrations were found to be significantly decreased in rhGH treated samples compared to placebo treated samples for measurements taken 1 day and eight days

Summary

Introduction

Apoptosis or “programmed cell death” is a physiologically favourable form of cell death which in addition to maintaining homeostatic control over cell populations, functions to remove damaged or diseased cells without incurring an inflammatory reaction [1,2] Mitochondrial mediated apoptotic signals are initiated by extracellular stimulation which serves to propagate the caspase response, demonstrating the key and central roles of mitochondrial organelles in apoptosis [3] Dysfunctional regulation of these apoptotic pathways is implicated in the development of pathological conditions such as cancer, diabetes, ischemia-reperfusion, autoimmune disorders, neurodegenerative diseases and acute organ failure [2,4,5,6]

Objectives

Results

Conclusion