Immunocytochemical evidence for intragranular processing of pro-opiomelanocortin in the melanotropic cells of the rabbit.

The immunogold technique, employing antisera with clear-cut specificities, was used to localise different processing stages of pro-opiomelanocortin (POMC) in rabbit melanotropic cells. While the antiserum against gamma 3-MSH labelled all the secretory granules including intrasaccular condensations in the Golgi apparatus, antisera against alpha-MSH only labelled extra-Golgi secretory vesicles (SV). All extra-Golgi SV were likewise labelled with the three antisera against alpha-MSH used, despite their different specificities for the deacetylated, N-acetylated or C-amidated forms of the peptide. The antibody against beta-endorphin also labelled the extra-Golgi SV, while only some SV were labelled with the antibody against gamma-endorphin. These results correlate with biochemical data in favour of mainly--if not exclusively--intragranular processing of POMC. Except for gamma 3-MSH, the cleavage of which could coincide with Golgi packaging of secretory material, other post-translational modifications of the precursor seem to occur when SV are discharged outside the Golgi area. The cleavage of gamma-endorphin appears to be a later step in POMC processing, occurring in some mature SV.