Identification of a receptor for N-POMC peptides

The adrenal cortex is a dynamic organ in which the cells of the outer cortex continually divide. It is well known that this cellular proliferation is dependent on constant stimulation from peptides derived from the ACTH precursor proopiomelanocortin (POMC) since disruption of pituitary corticotroph function results in rapid atrophy of the gland. Although ACTH has often been assumed to be the adrenal mitogen, results from our laboratory suggest that the true mitogen is a fragment derived from the N-terminal of POMC that does not contain the gamma-MSH sequence. Since these peptides are not generated during the processing of POMC in the pituitary it has been proposed that the mitogen is generated from circulating pro-gamma-MSH by an adrenal protease. We have recently substantiated this hypothesis by characterizing a serine protease expressed by the adrenal necessary for growth and lead us to propose that N-POMC (1-52) is the adrenal mitogen. Using N-POMC (1-28) linked to a solid support we have extended these studies in an attempt to identify the receptor through which this peptide elicits its actions. Using this approach we have isolated a 80 KDa candidate protein from membranes prepared from the adrenal cortical Y1 cell line.