Growth hormone (GH) action in the brain: neural expression of a GH-response gene

The presence of growth hormone (GH) binding sites and GH-receptor (GHR)-immunoreactive proteins in the brain suggests it is a target site for GH action. This could, however, reflect the presence of GH-binding proteins (GHBP) that are not linked to intracellular signal-transduction mechanisms, rather than authentic receptors. The possibility that GH has actions in the brain therefore has been examined by determining an intracellular mediator of GH action. The mechanism of GH action involves the induction of a number of specific GH-response genes. In chickens, a novel GH-responsive gene (GHRG-1) has been identified as an intracellular marker of GH action, since this gene is not expressed in GH-resistant dwarfs with dysfunctional GHRs and in normal chickens it is upregulated by exogenous GH. In normal chickens GHRG-1 mRNA is also abundant and widespread in the brain. In the cerebellum it is specifically localized in the cerebellar folia. It is present in most cells in the granular layers of the gray matter but is present in only a small number of scattered cells in the molecular layer and white matter. Intense labeling for GHRG-1 mRNA is also present in the large Purkinje cells and their dendrites at the interface between the molecular and granular layers. Labeling is also seen in the interneuronal basket cells projecting onto the Purkinje cells. In the mid-brain, cells in the ocular nerve complex and the tractus isthmo-opticus were strongly stained for GHRG-1 mRNA, with less intense staining in the central gray. In the hypothalamus, numerous small cells in periventricular locations and ependymal cells lining the III ventricle also label for GHRG-1 mRNA. These results clearly show, for the first time, the expression of a GH-responsive gene in neural tissues. Moreover, as GH- and GHR-immunoreactivity previously has been shown to be present in the same tissues expressing GHRG-1, it is possible that GH acts as an autocrine or paracrine within the CNS.