LOCALIZATION AND ONTOGENY OF GROWTH-HORMONE RECEPTOR GENE-EXPRESSION IN THE CENTRAL-NERVOUS-SYSTEM

There is literature evidence that both growth hormone (GH) and its med iator, insulin-like growth factor 1 (IGF-1), are able to act upon neur onal and glial cells in the brain. We report here the location of the GH receptor in the brain of the rat and rabbit. Receptor distribution was determined by immunohistochemistry with GH receptor/binding protei n (BP) specific monoclonal antibodies and by in situ hybridization wit h a S-35!riboprobe. GH receptor/BP immunoreactivity in the rat was mo st prominent in the neonate and declined with postnatal age. Receptor immunoreactivity was generalised with variation in immunoreactivity in regional areas. In the rat, strongest immunoreactivity was seen in la yers 2, 3, 5 and especially layer 6 of the cerebral cortex, in neurone s of the thalamus and hypothalamus, in Purkinje cells of the cerebellu m, in neurones of the trapezoid body of the brainstem, and in retinal ganglion cells. Glial cells, notably astrocytes were also strongly rea ctive, along with ependyma of the choroid plexus, ventricular lining a nd pia mater. In the neonatal rabbit, strongest immunoreactivity was e vident in layers 2 and 3 of the cerebral cortex, in pyramidal cells of the hippocampus, and in neurones of the inferior and superior collicu li, brain stem reticular formation, dorsal thalamus and hypothalamus. A similar distribution of GH receptor mRNA was seen by in situ hybridi zation. The ontogeny of GH receptor/BP mRNA in whole rat brain was qua ntified by solution hybridization-RNAse protection assay. Contrary to its ontogeny in the liver (Endocrinology, 113 (1983) 1325-1329) recept or mRNA decreased with postnatal age. This is the first description of divergent tissue specific ontogeny for the GH receptor/BP, and raises the possibility of a role for GH in influencing neuronal maturation a nd glial cell formation. Since there is evidence for GH synthesis with in the brain, and receptor distribution generally correlates with IGF- 1 expression, our findings raise the possibility of an endogenous GH-I GF-1 axis involved in brain growth and maturation.