Abstract
Adult rat chromaffin cells proliferate at a low rate throughout life and show robust mitogenic responses to a variety of agents in vivo and in vitro. Prolonged treatment of rats with some of these agents leads to development of pheochromocytomas, probably by exacerbating an age-dependent proclivity. The rat adrenal medulla is thus a remarkable model for studies of mitogenic signaling and neoplastic progression. Immunohistochemical approaches to the study of this model have helped to overcome obstacles presented by heterogeneity of the chromaffin cell population and complex relationships between medulla, cortex and nerve supply. Current evidence suggests that these relationships are important both in normal chromaffin cell turnover and in development of pheochromocytomas. The prototypical mitogen for adult rat chromaffin cells in vitro is nerve growth factor (NGF), which, parodoxically, arrests proliferation and causes neuronal differentiation of rat pheochromocytoma cells. Cell culture studies suggest that activation of phosphatidyl inositol 3-kinase by NGF is a critical determinant of mitogenic specificity in normal chromaffin cells. Numerous unanswered questions concern differences between normal chromaffin cells and their neoplastic counterparts, differences between chromaffin cells of rats and other species, and influences of the in vitro environment on responses to trophic signals.
