Structure and Regulation of the Mouse Melanin-Concentrating Hormone mRNA and Gene

doi:10.1006/mcne.1993.1035

Molecular and Cellular Neuroscience

Volume 4, Issue 3, June 1993, Pages 271-284

https://doi.org/10.1006/mcne.1993.1035 Get rights and content

Abstract

Melanin-concentrating hormone (MCH) and associated peptides, designated NEI and NGE, are predominantly expressed in hypothalamic neurons which project widely throughout the mammalian brain. These peptides might be involved as neuromodulators in the control of goal-directed behaviors, the integration of the stress response, and/or the regulation of arousal in general. In vivo studies of this peptidic system using a transgenic mouse model call for information about the structure and regulation of the mouse MCH (mMCH) gene. One complementary DNA (cDNA) for mouse prepro-MCH was isolated from a brain library by using a rat MCH cDNA as probe. This cDNA contains an open reading frame coding for a 165-amino acid precursor that displays about 90% sequence identity with rat and human prepro-MCHs. Most of the structural portion of the mMCH gene was cloned and characterized using the polymerase chain reaction (PCR). Strong conservation in exon-intron organization and primary sequences was found among the mouse, rat, and human genes, suggesting that coding and noncoding regions have important biological functions. Developmentally regulated expression of mMCH gene in mouse hypothalamus was examined by Northern blot hybridization. Up to 10-fold changes in the relative mMCH mRNA contents were observed during postnatal development, characterized by a peak at the weaning period. Moreover, striking variations in mMCH mRNA length, due to a poly(A) tail, were revealed during postnatal life. Tissue distribution of mMCH gene transcripts was investigated by means of the PCR and Northern blot procedures. Expression of the mMCH gene was revealed in heart, intestine, spleen, and testis and was found to be regulated in a developmentally programmed manner. Strikingly, short as well as long mMCH RNA species were identified at the periphery. Taken together, our data indicate that both transcriptional and post-transcriptional mechanisms regulate the expression of the MCH gene in mouse brain and at the periphery.

References (0)

Cited by (34)

Melanin-concentrating hormone and immune function
2009, Peptides
To date, melanin-concentrating hormone (MCH) has been generally considered as peptide acting almost exclusively in the central nervous system. In the present paper, we revise the experimental evidence, demonstrating that MCH and its receptors are expressed by cells of the immune system and directly influence the response of these cells in some circumstances. This therefore supports the idea that, as with other peptides, MCH could be considered as a modulator of the immune system. Moreover, we suggest that this could have important implications in several immune-mediated disorders and affirm that there is a clear need for further investigation.
Dynamic regulation of hypothalamic neuropeptide gene expression and food intake by melanocortin analogues and reversal with melanocortin-4 receptor antagonist
2005, Biochemical and Biophysical Research Communications
Citation Excerpt :
Indeed, AGRP is the endogenous antagonist of MC3R/4R [24,25], and α-MSH and AGRP are synthesized within an adjacent, but distinct, subgroup of hypothalamic neurons (POMC and AGRP neuron), which are sensitive to input from adiposity-related signals, most notably leptin [25–27]. Melanin-concentrating hormone (MCH), a neuropeptide highly expressed in the lateral hypothalamus (LH), functions as a critical regulator of feeding and energy balance, probably by acting downstream of leptin and the melanocortin system [28,29]. Our present study demonstrated that NPY and AGRP expression is rapidly regulated by the administration of NDP-MSH but also of [Gln6]α-MSH-ND and it is tempting to speculate that [Gln6]α-MSH-ND would regulate dynamically and closely these neuropeptides to respond rapidly to the needs of hypothalamic circuits linked to the control of food intake.
Melanocortins are known to be involved in the inhibition of food intake and energy metabolism. Acute and chronic intracerebroventricular administration of several different analogues of α-MSH, such as α-MSH, NDP-MSH, α-MSH-ND, [Gln⁶]α-MSH-ND, and [Lys⁶]α-MSH-ND, which were substituted in the position of His⁶ with Gln and Lys, and cyclic16k-MSH to C57J/BL6 mice resulted in a significant inhibition of both time course food intake and body weight gain, compared to the saline-administered control. However, [Gln⁶]α-MSH-ND(6–10), the truncated form of [Gln⁶]α-MSH-ND, had no inhibitory effects on food intake. In situ hybridization analysis revealed that the expression levels of AGRP and NPY in the hypothalamus were significantly and rapidly diminished while POMC expression was strongly induced by [Gln⁶]α-MSH-ND. Administration of JKC-363, a selective MC4R-specific antagonist, coupled with [Gln⁶]α-MSH-ND, specifically reversed the [Gln⁶]α-MSH-ND-induced inhibition of food intake, but also reversed the hypothalamic expression levels of neuropeptides such as AGRP, NPY, MCH, and POMC, which suggests [Gln⁶]α-MSH-ND can function as a selective MC4R agonist.
Possible involvement of melanin-concentrating hormone in food intake in a teleost fish, barfin flounder
2004, Peptides
We investigated the involvement of MCH in food intake in barfin flounder. The structure of barfin flounder MCH was determined by cDNA cloning and mass spectrometry. In fasted fish, the MCH gene expression and the number of MCH neurons in the brain were greater than controls. In white-reared fish, the MCH gene expression and the number of MCH neurons in the brain were greater than black-reared fish. Furthermore, white-reared fish grew faster than black-reared fish. These results indicate that a white background stimulated production of MCH and MCH, in turn, enhanced body growth, probably by stimulating food intake.
Human immune cells express ppMCH mRNA and functional MCHR1 receptor
2002, FEBS Letters
Citation Excerpt :
To our knowledge, we present here the first study reporting data demonstrating that MCH and its receptor MCHR1 can act as modulators of the immune system. Previously, the ppMCH and MCHR1 transcripts were observed in tissues like spleen or thymus but not in specific immune cells [9,10]. On base of RT-PCR analysis we showed the presence of the ppMCH and MCHR1 mRNA not only in mouse splenocytes and thymocytes but also in human tonsilar and blood cells.
Melanin-concentrating hormone (MCH) is highly expressed in the brain and modulates feeding behavior. It is also expressed in some peripheral tissues where its role remains unknown. We have investigated MCH function in human and mouse immune cells. RT-PCR analysis revealed a low expression of prepro-MCH and MCH receptor 1 (MCHR1) but not of MCHR2 transcript in tissular and peripheral blood immune cells. FACS and in vitro assay studies demonstrated that MCHR1 receptor expression on most cell types can trigger, in the presence of MCH, cAMP synthesis and calcium mobilization in peripheral blood mononuclear cells (PBMCs). Moreover, MCH treatment decreases the CD3-stimulated PBMC proliferation in vitro. Accordingly, our data indicate for the first time that MCH and MCHR1 may exert immunomodulatory functions.
Chapter II The melanin-concentrating hormone
2002, Handbook of Chemical Neuroanatomy
This chapter presents the most recent findings on structural analysis and neurobiology of melanin-concentrating hormone (MCH), with special emphasis on the cloning, functional characterization and neuronal distribution of at least two MCH receptors. It was a long-standing and important achievement. MCH is classified as a melanotropin—that is, a factor implicated in regulating color tegument. However, unlike the MSH and adrenocorticotropic hormone (ACTH) peptide family, all derived from the prepro-opio-melanocortin (POMC) precursor, MCH is not classified as a melanocortin because it lacks the consensus melanocortin sequence -His-Phe-Arg-Trp-. Consistent with that, MCH does not signal through the specific set of not less than six G-protein-coupled receptor (GPCR) proteins binding MSHs and ACTH, and termed from MC-1 to MC-6 binding. Intriguingly, it may be possible that MCH and MSH are evolutionary related.
Cloning of a novel G protein-coupled receptor, SLT, a subtype of the melanin-concentrating hormone receptor
2001, Biochemical and Biophysical Research Communications
A DNA fragment encoding an amino acid sequence possessing common features to the G protein-coupled receptor (GPCR) superfamily was found in the human genomic sequence, and from this information, the full-length cDNA of a novel GPCR, designated SLT, was cloned from the human hippocampus cDNA library. SLT showed the highest homology to the melanin-concentrating hormone (MCH) receptor, SLC-1 (31.5% identity), and to a lesser extent, to the somatostatin (SST) receptor subtypes. MCH exhibited agonistic behavior when applied to the SLT-expressing CHO cells at subnanomolar doses whereas more than 200 known peptides, including SST and cortistatin, did not. These results indicated that MCH is the cognate ligand of the SLT receptor and that this newly cloned GPCR is the second subtype of the MCH receptor. Quantitative polymerase chain reaction analysis of the SLT gene expression in human tissues showed that the SLT receptor is expressed mainly in brain areas including the cerebral cortex, amygdala, hippocampus, and corpus callosum, as well as in a limited number of peripheral tissues. The distribution of the SLT nearly overlapped that of SLC-1, suggesting that some of the neural functions of MCH may be mediated by both of these receptor subtypes.

View all citing articles on Scopus

View full text

Regular ArticleStructure and Regulation of the Mouse Melanin-Concentrating Hormone mRNA and Gene

Abstract

Regular Article
Structure and Regulation of the Mouse Melanin-Concentrating Hormone mRNA and Gene