Growth Hormone Modulates mRNA Expression of the GABA(B1) Receptor Subunit and GH/IGF Axis Genes in a Mouse Model of Prader-Willi Syndrome

Abstract

Objectives: The aim of this study was to investigate the effects of recombinant human GH (rhGH, henceforth designated GH) on the gene expression of GABA(B) receptor subunits and GH/insulin-like growth factor (IGF) axis genes IGF-I, IGF-1R, IGF-2 and IGF-2R in the brain regions of Prader-Willi syndrome (Snord116del) mice, a dwarf strain exhibiting cognitive impairment. Methods: Snord116del mice were treated with GH (1.0 mg/kg) or saline for seven days before decapitation and tissue dissection. The collected brain tissues were analysed for mRNA content using quantitative PCR (qPCR) in the cerebellum, hippocampus and cerebral cortex. Results: In the cerebellum, GH restored the mRNA expression level of the GABA(B1) receptor subunit (GABA(BRI)) and IGF-1R. Furthermore, a significant positive correlation was found between the level of GABABRI mRNA and the expression of the IGF-1R transcript. GH also induced an increase in the mRNA expression of IGF-2 and IGF-2R. Conclusions: These data suggest a modulatory effect of GH on the expression of GABA(BR1), and GH/IGF-1 axis genes in cerebellum may provide a mechanism for the GH-induced brain function in PWS patients.