The N-terminal fragment of pro-opiomelancortin (POMC) has been shown previously to act as an adrenal mitogen. However, little is known about the molecular mechanisms by which mitogenesis is stimulated, although it has been shown that N-POMC(1-28) stimulates the ERK pathway in human H295R cells. We have investigated signaling stimulated by N-POMC(1-28) and N-POMC(1-49) in the mouse Y1 cell line and found that both peptides stimulate ERK phosphorylation with maximal stimulation being achieved within 5min. Similar results were observed for both MEK and c-Raf phosphorylation, although N-POMC(1-49) stimulated the phosphorylation of Akt more robustly than N-POMC(1-28). We also investigated the expression of tyrosine kinase receptors in adrenal cells. PCR utilizing degenerate primers was performed on cDNA from both Y1 cells and rat adrenal tissue. Sequencing of 114 clones from each cDNA population revealed the expression of a number of receptors, several of which have not been described previously in the adrenal.