Do glucocorticoids induce adrenergic differentiation in adrenal cells of neural crest origin?

The chromaffin cells of the adrenal medulla originate in the neural crest and migrate to populate the emerging adrenal gland. When differentiated, the adrenal medulla is formed by two populations of cells: the norepinephrine (NE) cells, which contain the first 3 enzymes of the catecholamine pathway, and the epinephrine (Epi) cells, which contain all 4 enzymes. It has been suggested that in rat, the last enzyme, phenylethanolamine-N-methyltransferase (PNMT), appears in NE cells that are exposed to very high levels of fetal glucocorticoids (GCs), such as those present in the adrenal gland. If so, PNMT would appear during development after the initiation of fetal GC synthesis by the adrenal cortex at E18. In this study we examined the time of appearance and the relative level of PNMT mRNA and protein in rat embryos. We found (a) PNMT protein and mRNA are present at E16. Moreover, (b) the proportion of NE and Epi cells is already similar to that of adults and (c) the adult proportion of steady-state PNMT mRNA is also achieved prior to E18. We conclude that the appearance of PNMT is not affected by the surge of fetal GCs. Questions are raised as to the identity of the cues, genetic and/or epigenetic, which determine the differentiation of NE and Epi cells in the adrenal gland.