Human Pituitary Contains Dual Cathepsin L and Prohormone Convertase Processing Pathway Components Involved in Converting POMC into the Peptide Hormones ACTH α-MSH and β-Endorphin

摘要

The production of the peptide hormones ACTH, α-MSH, and β-endorphin requires proteolytic processing of POMC which is hypothesized to utilize dual cysteine and subtilisin-like protease pathways, consisting of the secretory vesicle cathepsin L pathway and the well-known subtilisin-like prohormone convertase (PC) pathway. To gain knowledge of these protease components in human pituitary where POMC-derived peptide hormones are produced, this study investigated the presence of these protease pathway components in human pituitary. With respect to the cathepsin L pathway, human pituitary contained cathepsin L of 27-29 kDa and aminopeptidase B of ∼64 kDa, similar to those in secretory vesicles of related neuroendocrine tissues. The serpin inhibitor endopin 2, a selective inhibitor of cathepsin L, was also present. With respect to the PC pathway, human pituitary expresses PC1/3 and PC2 of ∼60-65 kDa, which represent active PC1/3 and PC2; peptide hormone production then utilizes carboxypeptidase E (CPE) which is present as a protein of ∼55 kDa. Analyses of POMC products in human pituitary showed that they resemble those in mouse pituitary which utilizes cathepsin L and PC2 for POMC processing. These findings suggest that human pituitary may utilize the cathepsin L and prohormone convertase pathways for producing POMC-derived peptide hormones.