Growth hormone protects against kainate excitotoxicity and induces BDNF and NT3 expression in chicken neuroretinal cells.

There is increasing evidence to suggest a beneficial neuroprotective effect of growth hormone (GH) in the nervous system. While our previous studies have largely focused on retinal ganglion cells (RGCs), we have also found conclusive evidence of a pro-survival effect of GH in cells of the inner nuclear layer (INL) as well as a protective effect on the dendritic trees of the inner plexiform layer (IPL) in the retina. The administration of GH in primary neuroretinal cell cultures protected and induced neural outgrowths. Our results, both in vitro (embryo) and in vivo (postnatal), showed neuroprotective actions of GH against kainic acid (KA)-induced excitotoxicity in the chicken neuroretina. Intravitreal injections of GH restored brain derived neurotrophic factor (BDNF) expression in retinas treated with KA. In addition, we demonstrated that GH over-expression and exogenous administration increased BDNF and neurotrophin-3 (NT3) gene expression in embryonic neuroretinal cells. Thus, GH neuroprotective actions in neural tissues may be mediated by a complex cascade of neurotrophins and growth factors which have been classically related to damage prevention and neuroretinal tissue repair.

Expression, cellular distribution, and heterogeneity of growth hormone in the chicken cerebellum during development.

Although growth hormone (GH) is mainly synthesized and secreted by pituitary somatotrophs, it is now well established that the GH gene can be expressed in many extrapituitary tissues, including the central nervous system (CNS). Here we studied the expression of GH in the chicken cerebellum. Cerebellar GH expression was analyzed by in situ hybridization and cDNA sequencing, as well as by immunohistochemistry and confocal microscopy. GH heterogeneity was studied by Western blotting. We demonstrated that the GH gene was expressed in the chicken cerebellum and that its nucleotide sequence is closely homologous to pituitary GH cDNA. Within the cerebellum, GH mRNA is mainly expressed in Purkinje cells and in cells of the granular layer. GH-immunoreactivity (IR) is also widespread in the cerebellum and is similarly most abundant in the Purkinje and granular cells as identified by specific neuronal markers and histochemical techniques. The GH concentration in the cerebellum is age-related and higher in adult birds than in embryos and juveniles. Cerebellar GH-IR, as determined by Western blot under reducing conditions, is associated with several size variants (of 15, 23, 26, 29, 35, 45, 50, 55, 80 kDa), of which the 15 kDa isoform predominates (>30% among all developmental stages). GH receptor (GHR) mRNA and protein are also present in the cerebellum and are similarly mainly present in Purkinje and granular cells. Together, these data suggest that GH and GHR are locally expressed within the cerebellum and that this hormone may act as a local autocrine/paracrine factor during development of this neural tissue.