Endocrine

, Volume 35, Issue 3, pp 429–437

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

  • Vivian Hook
  • Lydiane Funkelstein
  • Thomas Toneff
  • Charles Mosier
  • Shin-Rong Hwang
Original Paper

DOI: 10.1007/s12020-009-9163-5

Cite this article as:
Hook, V., Funkelstein, L., Toneff, T. et al. Endocr (2009) 35: 429. doi:10.1007/s12020-009-9163-5

Abstract

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.

Keywords

ProteasesCathepsin LProhormone convertaseACTHβ-Endorphinα-MSHPOMC

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Vivian Hook
    • 1
    • 2
  • Lydiane Funkelstein
    • 1
  • Thomas Toneff
    • 1
  • Charles Mosier
    • 1
  • Shin-Rong Hwang
    • 1
  1. 1.Skaggs School of Pharmacy and Pharmaceutical SciencesUniversity of CaliforniaSan DiegoUSA
  2. 2.Departments of Neuroscience, Pharmacology, and Medicine, School of MedicineUniversity of CaliforniaSan DiegoUSA