Chromaffin cells in the adrenal medulla secrete the catecholamine hormones epinephrine and norepinephrine. These cells are derived during ebryonic development from the neural crest and are very similar to norepinephrine-secreting neurons in the sympathetic nervous system and the brain. Insulin-like growth factor-I (IGF- I) is a peptide hormone that is structurally similar to insulin but that probably acts to regulate cellular replication and differentiation. IGF-I enhances catecholamine secretion from bovine chromaffin cells in culture. The goal of this research is to understand the mechanism by which IGF-I regulates catecholamine secretion and other chromaffin cell functions. Because calcium is known to be an important regulator of catecholamine secretion, the proposed research will focus on the effects of IGF-I on calcium metabolism in chromaffin cells. The effects of IGF-I on the number and activity of calcium channels and on the concentration of intracellular calcium in chromaffin cells will be studied. If IGF-I affects the function of calcium channels in these cells, the channels that are regulated by IGF-I will be identified and characterized. The effects of IGF-I on other chromaffin cell functions, including catecholamine synthesis, cyclic AMP production, and phospholipid metabolism will be evaluated. This research should provide important new information about the regulation of catecholamine secretion and about the actions of IGF-I in the nervous system.
