Mammalian adrenal chromaffin cells coexpress the epinephrine-synthesizing enzyme and neuronal properties in vivo and in vitro.

Adrenal chromaffin cells and neurons of the sympathetic ganglia are derived from common precursors in the neural crest. The phenotype of the sympathoadrenal progenitor cell is unknown, but adult chromaffin cells are distinguished by the expression of phenylethanolamine-N-methyltransferase (PNMT) and the lack of neurofilament (NF) and neuritic processes. Mature neurons have processes and express NF, but are PNMT-. We hypothesize that embryonic adrenal cells are multipotential. This implies that the cells can coactivate all the traits characteristic of mature sympathetic neurons and chromaffin cells and then selectively extinguish expression of either the chromaffin or the neuronal traits, depending on the environment. We further asked whether this repression is plastic and can be environmentally modified in adult chromaffin cells. We demonstrate that, in vivo, embryonic (e-) rat adrenal cells coexpress PNMT and the intermediate- and high-molecular-weight neurofilaments at e-15.5 (21%), e-16.5 (40%), and e-20.5 (23%). When cultured in complete or glucocorticoid-depleted media for 5 to 14 days, 20% of adult bovine chromaffin cells which remain PNMT+ reexpress NF and extend NF+ and PNMT+ processes. Both the expression of NF and the extension of neurites are inhibited by the addition of 10(-7) M dexamethasone to complete media. We conclude that the embryonic adrenal medullary cells simultaneously express traits of mature chromaffin cells and neurons and that the phenotypes remain labile in the adult mammalian chromaffin cell. In addition, coexpression of PNMT, NF, and neurite extension are not mutually exclusive in either the embryonic or adult adrenal chromaffin cell.