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

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.

Exploring the mitochondrial microRNA import pathway through Polynucleotide Phosphorylase (PNPase)

“…With the mitochondrion playing a crucial role in providing energy and maintaining homeostasis in the cell, it is important to evaluate the impact that miRNAs have on mRNA and protein expression in the mitochondrion. MiRNAs localized to the mitochondrion have been found to target essential processes directly, such as energy metabolism, and indirectly such as apoptosis [27,28,50, 52,55,68]. The recent characterization of miRNA localization to various organelles within the cell, along with changes in miRNA species and levels during pathological states suggests a role in miRNA-mediated pathologic phenotypes [3,41,69].…”

Growth Hormone (GH) Administration Increases the Metabolic Activity of the left Hippocampus in an Elder Patient with Cognitive Disorders

“…Another possibility for explaining the findings we observed is that GH has produced an increase in brain flow in the patient, allowing greater uptake of FDG. Recently, we described that GH induces an important reparative effect on the endothelial dysfunction that appears after atherogenic stimuli, such as hypercholesterolemia [37]; moreover, the hormone is a mitochondrial protector [38][39], and atherogenesis is related to oxidative stress. Therefore, since the patient we treated had high levels of plasma cholesterol and triglycerides it is also possible that, despite the short time of treatment, GH may have contributed to improve the blood supply to the brain, facilitating the appearance of the changes here described (both in terms of PET-SCAN images and cognitive tests).…”

The Long Intron 1 of Growth Hormone Gene from Reeves’ Turtle (Chinemys reevesii) Correlates with Negatively Regulated GH Expression in Four Cell Lines

“…Its expression was significantly upregulated from fasting and downregulated after refeeding [ 43 ]. Moreover, the expression of miR-125b in mitochondrial fractions showed a significant downregulation after administration of recombinant human growth hormone [ 44 ].…”