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Pro‐Opiomelanocortin ( POMC ) Neurones, POMC ‐Derived Peptides, Melanocortin Receptors and Obesity: How Understanding of this System has Changed Over the Last Decade
Author(s) -
Mountjoy K. G.
Publication year - 2015
Publication title -
journal of neuroendocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.062
H-Index - 116
eISSN - 1365-2826
pISSN - 0953-8194
DOI - 10.1111/jne.12285
Subject(s) - melanocortin , melanocortin 3 receptor , melanocortins , melanocortin receptor , energy homeostasis , receptor , medicine , endocrinology , melanocortin 4 receptor , biology , signal transduction , leptin , hypothalamus , proopiomelanocortin , microbiology and biotechnology , biochemistry , obesity
Following the cloning of the melanocortin receptor and agouti protein genes, a model was developed for the central melanocortin system with respect to the regulation of energy and glucose homeostasis. This model comprised leptin regulation of melanocortin peptides and agouti‐related peptide (AgRP) produced from central pro‐opiomelanocortin (POMC) and Ag RP neurones, respectively, as well as Ag RP competitive antagonism of melanocortin peptides activating melanocortin 4 receptor (MC4R) to Gαs and the cAMP signalling pathway. In the last decade, there have been paradigm shifts in our understanding of the central melanocortin system as a result of the application of advanced new technologies, including Cre‐LoxP transgenic mouse technology, pharmacogenetics and optogenetics. During this period, our understanding of G protein coupled receptor signal transduction has also dramatically changed, such that these receptors are now known to exist in the plasma membrane oscillating between various inactive and active conformational states, and the active states signal through G protein‐dependent and G protein‐independent pathways. The present review focuses on evidence obtained over the past decade that has changed our understanding of POMC gene expression and regulation in the central nervous system, POMC and Ag RP neuronal circuitry, neuroanatomical functions of melanocortin receptors, melanocortin 3 receptor (MC3R) and MC 4R, and signal transduction through MC 3R and MC 4R.