THE MELANIN-CONCENTRATING HORMONE - FROM THE PEPTIDE TO THE GENE

Melanin-concentrating hormone (MCH) is a cyclic peptide originally iso lated from chum salmon pituitaries, then structurally characterized fr om rat hypothalami. In the fish, MCH induces melanin concentration wit hin the melanophores and may inhibit ACTH secretion in vitro and under stressful conditions in vivo. In the rat, MCH modulates ACTH release in vivo and oxytocin secretion in vitro. However, on the basis of neur oanatomical features, that is, cell bodies almost exclusively confined to the lateral area of the hypothalamus and the zona incerta, while f ibers are observed throughout whole rat or human brains, this peptide appears to participate as a neurotransmitter/neuromodulator in the con trol of goal-oriented behaviors and/or general arousal in mammals. The knowledge of structural and regulatory features of the MCH precursor, mRNA, and genes at the cellular and molecular levels has recently mad e great progress. (1) The cells expressing MCH and associated peptides have been defined conjointly using radioimmunoassay, immunocytochemis try, and in vitro and in vivo molecular hybridization techniques. (2) The organization of the precursor deduced from cDNA cloning has been e stablished and led to the discovery of two novel putative peptides nam ed NEI and NGE. (3) The regulation of MCH mRNA and peptide production has been explored during the course of development in rodent and human and under a variety of paradigms (neurogenic or osmotic stress, hormo nal stimuli, etc.). (4) The structure of the MCH genes has been determ ined in salmon, rat, mouse, and human and revealed striking exon-intro n organization differences between fish and mammals. Strong homology, with a likely functional implication, was found between salmon MCH mRN A and 7SL RNA, a structural RNA involved in protein translocation. Fur thermore, a variant gene that may encode slightly different MCH was fo und exclusively in primates. (5) Chromosomal assignment of the authent ic and variant MCH genes in rat and human indicates that these genes m ay be good candidates involved in neurodegenerative or psychiatric dis orders. Based on the framework of these studies, a working model of MC H regulation/function in mammalian brain is finally proposed.