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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

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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.

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Acknowledgments

The authors appreciate support of this research by the National Institutes of Health. Assistance for this project by D. Tierney is acknowledged.

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Authors and Affiliations

  1. Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, 9500 Gilman Dr. MC 0744, La Jolla, San Diego, CA, 92093-0744, USA

    Vivian Hook, Lydiane Funkelstein, Thomas Toneff, Charles Mosier & Shin-Rong Hwang

  2. Departments of Neuroscience, Pharmacology, and Medicine, School of Medicine, University of California, La Jolla, San Diego, CA, USA

    Vivian Hook

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  1. Vivian Hook
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  2. Lydiane Funkelstein
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Correspondence to Vivian Hook.

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Hook, V., Funkelstein, L., Toneff, T. et al. 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. Endocr 35, 429–437 (2009). https://doi.org/10.1007/s12020-009-9163-5

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  • DOI: https://doi.org/10.1007/s12020-009-9163-5

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