Basic fibroblast growth factor modulates insulin-like growth factor-I, its receptor, and its binding proteins in hypothalamic cell cultures.

ABSTRACT

Interactions between different growth factors may be important in the regulation of cell growth and differentiation in the nervous system. For instance, basic fibroblast growth factor (bFGF) regulates neuroblast division through a mechanism probably involving insulin-like growth factor-I (IGF-I). In this regard, we previously found that simultaneous addition of both factors produces an additive effect on survival and differentiation of hypothalamic neuronal and glial cells in culture. To further analyze these interactions, we explored the influence of bFGF on IGF-I, its membrane receptor, and its binding proteins in hypothalamic cells. We also tested the effects of IGF-I on its own receptor and binding proteins (IGFBPs) to determine the specificity of bFGF's actions. Treatment of neuronal and glial cultures with bFGF produced an increase in IGF-I receptors, without changing their affinity, together with an increase in the apparent M(r) of the receptor. On the other hand, IGF-I elicited a down-regulation of its own receptor in both neurons and glia, without modifying its affinity. Treatment with bFGF also produced a marked differential effect on the IGFBPs secreted by the cells. While IGFBP levels in neuronal cultures were greatly increased by bFGF, their production by glial cells was inhibited. On the other hand, IGF-I increased the amount of IGFBPs in both types of cells. Finally, addition of bFGF to the cultures elicited a dose-dependent increase in the release of IGF-I to the medium, but only a moderate increase in cellular IGF-I content, in both neurons and glia. We conclude that bFGF strongly modulates IGF-I, its receptors, and its binding proteins in the two major cell types of the hypothalamus. These findings reinforce the possibility that IGF-I and/or its receptors and binding proteins are involved in the trophic effects of bFGF on developing brain cells.