DHEA reduces NGF-mediated cell survival in serum-deprived PC12 cells.

Adrenocortical androgens, including dehydroepiandrosterone (DHEA), are produced in the inner zone of the adrenal cortex that is in direct contact with the neural crest-derived catecholamine-producing chromaffin cells. DHEA has recently been identified as a crucial regulator of neuronal stem cell proliferation. Thus, DHEA might play a hitherto unknown role in intra-adrenal tissue formation. In the present study, we examined the influence of DHEA on nerve growth factor (NGF)-mediated survival in serum-deprived PC12 cells and analyzed the influence of DHEA on NGF-induced ERK1/2 mitogen-activated protein (MAP) kinase activation by enzyme-linked immunosorbent assay (ELISA). Cell survival promoted by NGF in serum-deprived PC12 cells and neurite outgrowth was reduced by DHEA, pointing toward a role of DHEA in the differentiation process of chromaffin cells. Furthermore, NGF-induced ERK 1/2 activation was significantly inhibited by DHEA. Hence, we speculate that DHEA might influence NGF-mediated chromaffin differentiation processes using the ERK1/2 MAP kinase pathway during adrenal tissue development.