title: Human pituitary contains dual cathepsin L and prohormone convertase processing pathway components involved in converting POMC into the peptide hormones ACTH, alpha-MSH, and beta-endorphin.
abstract: The production of the peptide hormones ACTH, alpha-MSH, and beta-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 approximately 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 approximately 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 approximately 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.
authors.affiliation: Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, La Jolla, San Diego, CA 92093-0744, USA. vhook@ucsd.edu
authors.forename: Vivian
authors.initials: V
authors.lastname: Hook
authors.forename: Lydiane
authors.initials: L
authors.lastname: Funkelstein
authors.forename: Thomas
authors.initials: T
authors.lastname: Toneff
authors.forename: Charles
authors.initials: C
authors.lastname: Mosier
authors.forename: Shin-Rong
authors.initials: SR
authors.lastname: Hwang