Autoradiographic and immunohistochemical localization of insulin-like growth factor-I receptor binding sites in brain of the brown trout, Salmo trutta

Abstract

Insulin-like growth factor-I (IGF-I), a peptide closely related to insulin, is known to play crucial roles in brain development. While the central sites of action of IGF-I in higher vertebrates are now well established, surprisingly little is known in the teleost model where the brain undergoes continual, indeterminate, growth. In this study, we have mapped the distribution of putative IGF-I receptor (IGF-IR) binding sites in the brain of the brown trout using both ligand binding in vitro autoradiography and immunohistochemistry. The presence of IGF binding proteins (IGFBPs) was further studied by competitive inhibition using unlabelled IGF-I and des-(1-3)-IGF-I. In both juvenile and adult trout brain, [125I]IGF-I binding was highest in cerebellum and optic tectum, both regions of the teleost brain known to grow the most actively throughout life. At the cellular level, IGF-IR immunoreactivity was confirmed on cell bodies and dendrites, particularly of larger presumptive neurons including purkinje cells and dendritic fibres throughout the molecular layer of the cerebellum. Abundant IGF-IR expression in hypothalamic regions may further be related to neuron growth while a possible hypophysiotropic role will require further investigation. Competitive inhibition studies employing des-(1-3)-IGF-I also suggest IGFBPs are present in all regions exhibiting high [125I]IGF-I ligand binding and confirms the presence of this important regulatory component of the IGF-I system in the teleost brain. The importance of the IGF-I system in brain development, particularly in regions such as the cerebellum, together with the continual lifetime growth of the fish central nervous system, suggest the teleost brain is an extremely useful site for studying the actions of IGF-I in relation to neuron proliferation, growth, and survival in an adult brain.