Abstract
Proopiomelanocortin (POMC) undergoes extensive and tissue-specific posttranslational processing to yield a range of biologically active peptides. Historically, the most clearly defined roles of these peptides are in the control of adrenal steroidogenesis by corticotroph-derived ACTH and skin pigmentation by alphaMSH. However, a rapidly expanding body of work has established that POMC-derived peptides synthesized in neurons of the hypothalamus play a central role in the control of energy homeostasis. We review how inherited abnormalities in POMC synthesis and processing and defects in the action of POMC-derived peptides in both humans and mice have helped shape our current understanding of the importance of the melanocortin system in human energy balance.
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