Recombinant Human Growth Hormone Affects the Density and Functionality of GABA_B Receptors in the Male Rat Brain

Abstract

The beneficial effects of growth hormone (GH) on memory and learning have previously been confirmed in both humans and in animal models. An important role of GABA_B receptors for multiple forms of learning and memory has also been reported. In this study, we examined the effect of GH on the density and functionality of the metabotropic GABA_B receptors in the rat brain. Male Sprague-Dawley rats (n = 24) divided into 3 groups were injected twice daily with recombinant human GH (0.07 or 0.7 IU/kg) for 7 days. The effects of the hormone were determined by quantitative autoradiography and by GABA_B stimulated [³⁵S]-GTPγS binding using the selective GABA_B receptor agonist baclofen. The results demonstrate moderate but significant alterations in both receptor density and functionality in a number of brain regions. For example, a dose-dependent upregulation of GABA_B receptors was found in the cingulate cortex, primary motor cortex and caudate putamen, whereas attenuation in the receptor density was encountered in, for example, the medial geniculate nucleus. Although the GH-induced effects on the GABA_B receptor in brain areas associated with cognition were fairly pronounced, they were significant and we propose that the physiological responses observed after GH administration at least partly can be mediated through a mechanism involving GABA_B receptors.

Treatment with Growth Hormone (GH) Increased the Metabolic Activity of the Brain in an Elder Patient, Not GH-Deficient, Who Suffered Mild Cognitive Alterations and Had an ApoE 4/3 Genotype

“…An additional clinical trial of the same group carried out on 30 adults (age 55–87 years, 17 with MCI), using the same GHRH analog at the same doses and time, showed that this treatment significantly increased gamma-aminobutyric levels acid (GABA) in three brain regions of the left side (frontal dorsolateral, posterior cingulate, and posterior parietal), increased N -acetylaspartylglutamate in the frontal cortex, and decreased myoinositol (an osmolyte related to AD) in the posterior cingulate, inducing a positive effect on cognition in both groups of participants without affecting the regulation of plasma glucose [73]. However, in that study, no changes were found in brain glutamate levels, unlike what has been reported in preparations of hippocampal cuts from old rats treated with GH or IGF-I [32], but consistent with the effects of GH on the density and functionality of GABAB receptors in male rats in areas of the brain related to cognition [74]. These data seem to support our findings using GH in this study because although it cannot be discarded that GHRH exerts its own effects at the brain level, as it seems to do in other territories, it is clear that the administration of GHRH or one of its analogues induces the release of GH [75].…”

Synaptic plasticity in the anterior cingulate cortex in acute and chronic pain

“…Finally, metabotropic glutamate receptors (mGluRs) can modulate synaptic transmission in the ACC 34 . As elsewhere in the cortex, GABA is the major inhibitory transmitter in the ACC, where it acts on both type A GABA (GABA A ) receptors 35 and GABA B receptors 36,37 . Activation of GluK1-containing kainate receptors in the ACC can regulate GABA release 35 .…”

The Effect of Growth Hormone on mRNA Expression of the GABAB1Receptor Subunit and GH/IGF Axis Genes in a Mouse Model of Prader-Willi Syndrome

“…GABA B receptor has been reported to be important for neuronal excitability and plasticity and is suggested to be involved in the regulation of long-term potentiation, which is the cellular mechanism for learning and memory 15,20) . GH treatment affects the functionality and density of GABA B receptors in the area of the brain associated with cognition 16) . Other studies have revealed that GH treatment up-regulated the expression of GABA BR1 transcript in rat brain, suggesting a connection between GH and the GABA B system 17,21) .…”

“…The functional GABA B receptors consist of two subunits, GABA BR1 and GABA BR2 13) , which are responsible for the neuromodulatory effect of GABA 14,15) . Recently, exogenous GH has been reported to increase the abundance of the GABA B receptor in rat brain 16) and GABA BR1 gene expression in hypophysectomised rat 17) . These findings suggest a possible correlation between GH-induced cognitive function and the GABA B receptor.…”