Abstract

The cloning of the bovine proopiomelanocortin cDNA in 1978 by Nakanishi and colleagues was the result of a remarkable series of exacting and ingenious experiments. With this work they instantly confirmed the single precursor hypothesis for ACTH-β-lipotropin, as it was then known, and in so doing revealed the existence of additional, largely unpredicted, N-terminal peptides that together formed the proopiomelanocortin (POMC) precursor peptide. This work paved the way for a host of additional studies into the physiology of these peptides and their regulation. Furthermore the cloning of the murine Pomc gene was essential for subsequent studies in which Pomc was intentionally deleted in the mouse illuminating its substantial role in body weight regulation and adrenal function. Contemporaneously with this work, naturally occurring mutations in human POMC came to light underlining the vital role of this gene in appetite regulation. In this article I review each of these aspects of POMC with the benefit of several decades of hindsight and informed by more recent genomic and transcriptopic data.