Development and plasticity of adrenal chromaffin cells: cues based on in vitro studies

Neural crest derived precursors of the sympathoadrenal cell lineage give rise to two major cell types that differ in a number of morphological, ultrastructural, and biochemical characteristics: principal sympathetic neurons and chromaffin cells of the adrenal medulla. The present article reviews experimental studies performed on cultured adrenal medullary cells and designed to unravel the nature of epigenetic signals governing the developmental choice between the endocrine chromaffin and the neuronal sympathetic phenotype. Emphasis is placed on the role of glucocorticoids in initiation, development, and maintenance of the endocrine chromaffin phenotype and apparently antagonistic influences exerted by nerve growth factor (NGF) in vitro, resulting in the acquisition of neuronal properties by differentiated chromaffin cells. Experimental data from in vitro studies are compatible with the following conclusions. Glucocorticoids represent the decisive signal for the initial induction of endocrine differentiation. Moreover, high steroid hormone concentrations, as present in the adrenal medulla, are a prerequisite for the maturation of chromaffin cells. Even in a differentiated state, the endocrine phenotype is unstable in the absence of glucocorticoids, and the cells seem to reenter the neuronal developmental pathway. Under these conditions, cellular survival and differentiation into sympathetic neurons become NGF-dependent, as in normal sympathetic development. Thus, the effects of NGF survival, neurite outgrowth, and transmitter synthesis of cultured chromaffin cells probably do not reflect the induction of a specific phenotype, but they may be interpreted as a general neurotrophic support observable with other responsive cell types.