Immunohistochemical localization of growth hormone receptor binding protein in the mammalian cerebellum

Abstract

A panel of monoclonal antibodies to the growth hormone (GH) receptor/binding protein was used to demonstrate the existence and detail the expression of GH receptors in the cerebellum of 2, 10, 28 days old postnatal and adult rats and 10, 20 days old and adult rabbits by immunohistochemistry to define potential targets for endogenous GH action in the cerebellum. Receptors were localized in membrane and cytoplasmic components of neurons and glial cells and expression decreased with age. Intense immunoreactivity was observed in the cytoplasm and dendrites of Purkinje cells and in cells of the cerebellar nuclei. Glial cells also showed receptor expression. Strong immunoreactivity was observed with two monoclonal antibodies and lesser reactivity was seen with others, paralleling their affinities for the receptor. The cytoplasmic presence of this putatively plasma membrane located GH receptor is accounted for by the high receptor content of endoplasmic reticulum and the existence of a soluble form of the GH receptor, namely the GH binding protein (BP) derived from the membrane receptor by cleavage, and receptor localization reported here correlate well with the distribution of insulin-like growth factor 1 (IGF-1) mRNA and immunoreactivity in cerebellar Purkinje cells and glial cells. Primary localization of the receptor in the cerebellum is in direct contradiction to both classical GH action and the somatomedin hypothesis and supports and extends the theory of genetically regulated macroneuronal maturation.