Characterization of a serine protease that cleaves pro-gamma-melanotropin at the adrenal to stimulate growth

The adrenal gland requires stimuli from peptides derived from the ACTH prec ursor, pro-opiomelanocortin (POMC), to maintain its tonic state. Studies ha ve proposed that a specific postsecretional cleavage of the nonmitogenic N- terminal 16 kDa fragment, also known as pro-gamma -melanotropin (pro-gamma -MSH), is required, releasing shorter fragments that promote adrenal growth . Here, we provide evidence for this hypothesis by the cloning and characte rization of a serine protease that is upregulated during growth of the adre nal cortex. It is expressed exclusively in the outer adrenal cortex, the si te of cell proliferation, and in the Y1 adrenal cell line. We also show tha t it is required for growth of Y1 cells, remains bound to the cell surface, and cleaves its substrate, pro-gamma -MSH, at a specific bond.