MCH or melanin concentrating hormone is a cyclic 19 amino acid hypothalamic neuropeptide produced by neurons in the lateral hypothalamus and the zona incerta in humans. Crit Rev Neurobiol. 1994;8(4):221-62. MCH was initially described as a factor that mediates colour change in teleost fish and named melanophore concentrating hormone accordingly. Nature. 1983 Sep 22-28;305(5932):321-3. MCH acts on melanosomes (neuroectoderm derived cells) which contain melanophores (pigment containing vesicles), to produce aggregation or dispersion with resultant changes in refractive index of the scales of fish. alpha-MSH produces darkening (dispersion of melanophores) while MCH produces lightening (aggregation of melanophores) in fish, although no such function has been described in humans for MSH. Mammalian MCH is derived from the larger pre-pro-hormone precursor of MCH coded for by the pMCH gene. The pre-pro-hormone precursor is proteolytically cleaved into MCH and another peptide named MGOP (MCH Gene-Overprinted Polypeptide) as well as two other neuropeptide products namely NEI (neuropeptide E-I) and NGE (neuropeptide G-E). Endocrinology. 1989 Oct;125(4):2056-65. MCH immunoreactive fibres are seen in the lateral posterior hypothalamic area and the peri-fornical area. In the periphery, MCH is expressed in testis, stomach, intestine, Neuroendocrinology.1995 Apr;61(4):348-64. immune cells FEBS Lett. 2002 Sep 11;527(1-3):205-10. and the skin. Biochem Biophys Res Commun. 2002 Aug 23;296(3):698-701
Two G-protein coupled receptors have been described for MCH; Trends Endocrinol Metab. 2000 Oct;11(8):299-303 MCHR1 and MCHR2 J Biol Chem. 2001 Jun 8;276(23):20125-9 . MCHR1 was found to be identical to the SLC-1 orphan receptor, and its gene was localised to chromosome 22q13.3 FEBS Lett. 1996 Dec 2;398(2-3):253-8. The MCHR1 receptor is highly conserved between humans and rodents. MCHR1 _expression is highest in the brain (cortex, basal ganglia, hypothalamus, brainstem) with lower _expression in eye, tongue, adipose tissue and muscle. Nature. 1999 Jul 15;400(6741):265-9. In the brain, high levels of MCHR1 _expression is seen in the olfactory areas, amygdala, hippocampus, as well as the arcuate and ventromedial nuclei of the hypothalamus, the latter two being areas involved in regulation of energy balance.
MCHR2 is also expressed in similar areas in the brain with high _expression in the frontal cortex, amygdala and nucleus accumbens. Proc Natl Acad Sci U S A.2001 Jun 19;98(13):7576-81; Proc Natl Acad Sci U S A. 2001 Jun 19;98(13):7564-9 ; J Biol Chem. 2001 Jun 8;276(23):20125-9 .as well as the intestine, prostate and adipose tissue J Biol Chem. 2001 Jun 8;276(23):20125-9. Rodents do not have the MCHR2 receptor making it difficult to assess its functional importance in man. Genomics. 2002 Jun;79(6):785-92. Dogs and monkeys have both MCHR1 and MCHR2.
MCH regulation and actions
MCH mRNA is elevated in leptin-deficient ob/ob mice compared to controls suggesting that leptin negatively regulates MCH. Nature. 1996 Mar 21;380(6571):243-7. MCH mRNA levels are increased in response to fasting in both normal and ob/ob animals. This fasting induced increase is blunted with leptin therapy in both animals. Beta 3 adrenergic receptor agonists produce anorexia with a fall in leptin levels and an increase in MCH mRNA. Diabetes. 1996 Jul;45(7):909-14.
Injection of MCH intracerebroventricularly or directly into the paraventricular nucleus Brain Res. 1999 Nov 6;846(2):164-70.increases food intake. Chronic infusions into the lateral ventricle also resulted in hyperphagia and weight gain. Int J Obes Relat Metab Disord. 2002 Oct;26(10):1289-95. Transgenic over-_expression of MCH produces hyperphagia with weight gain when mice were maintained on a high fat diet. J Clin Invest. 2001 Feb;107(3):379-86 Mice lacking MCH (MCH knock out mice) are lean Nature. 1998 Dec 17;396(6712):670-4. with reduction in feeding and increased energy expenditure. MCHR1 antagonists reduce food intake and produce weight loss in diet induced obese rats. Nat Med. 2002 Aug;8(8):825-30 MCHR1 knock out mice show increased metabolic rate and resistance to diet induced obesity but demonstrate hyperphagia. Proc Natl Acad Sci U S A. 2002 Mar 5;99(5):3240-5 This paradoxical hyperphagia needs to be clarified. MCH antagonizes the anorectic effect of alpha MSH. Am J Physiol. 1998 Apr;274(4 Pt 1):E627-33.