IMMUNOHISTOCHEMICAL LOCALIZATION OF GROWTH-HORMONE RECEPTOR-BINDING PROTEIN IN THE MAMMALIAN CEREBELLUM

A panel of monoclonal antibodies to the growth hormone (GH) receptor/b inding protein was used to demonstrate the existence and detail the ex pression of GH receptors in the cerebellum of 2, 10, 28 days old postn atal and adult rats and 10, 20 days old and adult rabbits by immunohis tochemistry to define potential targets for endogenous GH action in th e cerebellum. Receptors were localized in membrane and cytoplasmic com ponents of neurons and glial cells and expression decreased with age. Intense immunoreactivity was observed in the cytoplasm and dendrites o f Purkinje cells and in cells of the cerebellar nuclei. Glial cells al so showed receptor expression. Strong immunoreactivity was observed wi th two monoclonal antibodies and lesser reactivity was seen with other s, paralleling their affinities for the receptor. The cytoplasmic pres ence of this putatively plasma membrane located GH receptor is account ed for by the high receptor content of endoplasmic reticulum and the e xistence of a soluble form of the GH receptor, namely the GH binding p rotein (BP) derived from the membrane receptor by cleavage, and recept or localization reported here correlate well with the distribution of insulin-like growth factor 1 (IGF-1) mRNA and immunoreactivity in cere bellar Purkinje cells and glial cells. Primary localization of the rec eptor in the cerebellum is in direct contradiction to both classical G H action and the somatomedin hypothesis and supports and extends the t heory of genetically regulated macroneuronal maturation.