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

• Published in: Endocrine Vol. 35; no. 3; pp. 429 - 437
• Main Authors: Hook, Vivian, Funkelstein, Lydiane, Toneff, Thomas, Mosier, Charles, Hwang, Shin-Rong
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.06.2009
• Subjects: Adrenocorticotropic Hormone - analysis; Adrenocorticotropic Hormone - metabolism; alpha-MSH - analysis; alpha-MSH - metabolism; beta-Endorphin - analysis; beta-Endorphin - metabolism; Cathepsin L; Cathepsins - metabolism; Cysteine Endopeptidases - metabolism; Diabetes; Endocrinology; Humanities and Social Sciences; Humans; Internal Medicine; Medicine; Medicine & Public Health; Metabolic Networks and Pathways - physiology; Models, Biological; multidisciplinary; Original Paper; Peptide Hormones - analysis; Peptide Hormones - metabolism; Pituitary Gland - chemistry; Pituitary Gland - enzymology; Pituitary Gland - metabolism; Pro-Opiomelanocortin - metabolism; Proprotein Convertases - metabolism; Science; POMC; Prohormone convertase; Cathepsin L; Proteases; ACTH; β-Endorphin; α-MSH
• ISSN: 1355-008X; 1559-0100
• DOI: 10.1007/s12020-009-9163-5

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.