• Archives of Pharmacal Research
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• v.16 no.4
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• pp.276-282
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• 1993

This study has been undertaken to examine the effect of 3-methylcholanthrene (3MC) on rat uterine growth and to understand the mechanism of action of 3MC in rat uterus. After diethylstilbesterol(DES) or tamoxifen(TAM) or 3MC or DES plus TAM or DES plus 3MC was administered into immature female rats, uterine weight over corn oil-treated uteri. 3MC treatment had no effect on uterine weight but, DES stimulated uterine weight was inhibited by 3MC concomitant tratment. While TAM alone treatment showed slight increase in uterine wieght, inhibited uterine growth simulated by DES when it was adiministrated with DES condirect binding assay with $[^3H]$ estradiol and the relative binding affinities of 3MC and TAM were estimated by competetion assy. Estradiol tumed out to have high affinity for rat uterine estrogen receptor (kd = 0.4 nM). The relative binding affinities of TAM and 3MC were 1% and 4.7% that of DES for rat uterine estrogen receptor, respectively. 3MC was shown to have similar affinity for eat uterine estrogen receptor to that of TAM. Effects of DES 3MC and TAM administration in vivo on rat uterine estrogen recptor level were examined. It was confirmed that the estrogen, DES and antiestrogen, TAM decreased estrogen receptor levels from rat ulterus and also 3MC decreased rat uterine estrogen receptor level when rats were treated with DES, TAM and 3MC in vivo. Data indicates that 3MC acts as an antiestrogen mediated through estrogen receptor system.

• Fisheries and Aquatic Sciences
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• v.13 no.4
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• pp.263-271
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• 2010

G protein-coupled receptors (GPCR) constitute the largest superfamily of cell membrane receptors, mediating diverse signal-transduction pathways. The melanocortin 4 receptor (MC4R) has been of interest for its physiological role and size, one of the smallest among the GPCRs, which makes it a good model system for the structural study of GPCRs. To study the molecular structure and tissue-specific expression of MC4R in olive flounder (Paralichthys olivaceus), the full-length MC4R gene was obtained using PCR amplification of genomic DNA as well as cDNA synthesis. Sequence analysis of the gene indicates that 978 bp of the MC4R gene encodes 325 amino acids without introns. Sequence alignment with the MC4Rs from other fish shows the highest degree of identity (96%) between Paralichthys olivaceous and Verasper moseri, followed by Takifugu rubripes and Tetraodon nigroviridis (89%). RNA was isolated from various tissues to examine the tissue distribution of MC4R by using RT-PCR. The results showed major expression of MC4R in the liver, brain, and eye, which is consistent with the expression pattern in other fish belonging to the order Pleuronectiformes.

• Journal of Animal Science and Technology
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• v.49 no.4
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• pp.437-442
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• 2007

The melanocortin-4 receptor(MC4R) is virtually expressed in all brain regions and plays an important role in energy homeostasis in mammals. MC4R has been intensively studied as a trait gene controlling economically important traits, such as growth and feed conversion, etc. Six hundreds and sixty Duroc pigs were genotyped for the MC4R locus and analyzed their relationships with breeding values for average daily gain(ADG), backfat thickness(BF), days to 90kg(D90) and feed conversion(FC). The estimated genotype frequencies for the all Duroc pigs were: 30.8%, 45.2%, 24.1% for AA, AB and BB genotypes, respectively. The mutant A allele was significantly associated with ADG, D90 and BF whereas no significant relationship was found with FC. The change of gene frequencies by generation was shown in both selected and culled groups. These results indicate that the MC4R polymorphism could be integrated in the present selection program to realize a marker-assisted selection for the growth traits of the Duroc population.

• Genes and Genomics
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• v.40 no.11
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• pp.1119-1125
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• 2018

Melanocortin 4 receptor: (MC4R) and Myostatin (MSTN) are two important growth trait-related genes in animals. In this study, we showed that two SNPs, MC4R-719A>G and MSTN-519C>T, found in the promoters of the MC4R and MSTN genes, respectively, are both associated with growth traits in Spinibarbus hollandi. Furthermore, we observed that there were significant associations between the expression levels of the MC4R and MSTN genes and these two growth trait-related SNPs. The expression level of MC4R gene in brain was lower in GG genotype fish with extremely high growth performance than that in AA genotype fish with extremely low growth performance. Expression level of the MSTN gene in muscle was lower in TT genotype fish with extremely high growth performance than that in CC and CT genotype fish with lower growth performance. The results indicated that these SNPs located in the promoters of MC4R and MSTN are associated with growth-related traits through modification of gene expression levels. The MSTN and MC4R SNPs may have useful application in effective marker-assisted selection aimed to increase output in S. hollandi.

• Journal of Life Science
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• v.15 no.6 s.73
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• pp.968-971
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• 2005

The Melanocortin-4 receptor gene (MC4R) regulates the energy balance and the genetic basis of obesity. A polymorphism in the porcine melanocortin-4 receptor has previously shown to be associated with growth, fat deposition and feed intake. In this study, the polymorphism of the gene was studied in several pig breeds of Duroc, Landrace, Berkshire, and Yorkshire. The results showed that the frequencies of MC4R genotype varied among those breeds. Association analyses were also performed between the MC4R polymorphism and average daily gain, feed conversion ratio, backfat thickness and lean percentage phenotypes. The results strongly support that the MC4R polymorphism can be used DNA marker selection indicator for economically important traits for pig breeding program in Korea.

• Clinical Nutrition Research
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• v.13 no.3
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• pp.214-225
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• 2024

Polymorphisms in the melanocortin 4 receptor (MC4R) gene with occurrence and progression of chronic diseases such as obesity and cardiovascular disease (CVD) have long been addressed but there is a lack of evidence for complex interrelationships, including direct and indirect effects of these variables. This review specifically focuses on studying the effects of healthy diet interaction and MC4R polymorphisms on the development of CVD. The quantity and quality of carbohydrates and proteins consumed are related to obesity susceptibility and cardiometabolic risk factors. A healthy dietary pattern such as a Mediterranean dietary can modulate the association between MC4R polymorphisms (rs17782313) and the risk of CVDs. Also, the Nordic diet can reduce lipid profiles such as low-density lipoprotein cholesterol (LDL-C) and total cholesterol levels. On the other hand, MC4R interaction with the dietary inflammatory index decreases high-density lipoprotein cholesterol levels and increases LDL-C and triglyceride (TG) levels. Additionally, the DASH diet decreases TG, atherogenic index of plasma, systolic blood pressure, diastolic blood pressure, and serum glucose. The interaction between MC4R genes and diets plays an important role in the development of CVD. Adherence to healthy diets such as the Mediterranean, Nordic, Anti-inflammatory, and Dash diets might be an efficient strategy to prevent CVD. The potential for personalized diets to be developed for the treatment and prevention of CVD and its related comorbidities is expected to expand as this field develops.

• Journal of the Korean Magnetic Resonance Society
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• v.16 no.1
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• pp.34-45
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• 2012

Melanocortin-4 receptor (MC4R) subtype is associated with obese humans. Especially, in a patient with severe early-onset obesity, novel heterozygous mutation in the MC4R gene was detected, resulting in an exchange of aspartic acid to asparagine in $90^{th}$ amino acid residue located in the predicted second trans-membrane domain (TM2). Mutations in the melanocortin-4 receptor (MC4R) gene are the most frequent monogenic causes of severe obesity which have been described as heterozygous with loss of function. In order to compare structure difference between MC4R wild type (MC4R-TM2-wt) and mutant (MC4R-TM2-D90N), we designed both MC4R-TM2-wt and MC4R-TM2-D90N construct in pET 21b vector. In this study, we optimized high-yield purification procedure for recombinant TM2-D90N. Eluted recombinant protein was resolubilized under urea condition for thrombin cleavage reaction and we conducted the high-performance liquid chromatography (HPLC) with reverse phase column under 1% acetonitrile, 0.01% TFA buffer solution. The molecular size of purified target peptide was confirmed by Tricine-SDS page analysis. To characterize MC4R-TM2-D90N, we have performed $^{15}N$-isotope labeling of peptide using M9 media and purified labeled target peptide for hetero-nuclear NMR spectroscopy.

• Asian-Australasian Journal of Animal Sciences
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• v.19 no.6
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• pp.763-768
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• 2006

Genetic and pharmacological studies in mice have demonstrated a complementary role for the melanocortin 4 receptor (MC4R) in the control of food intake, energy balance and body weight. This study was designed to investigate the associations of a MC4R gene polymorphism on chicken growth and body composition traits in broiler lines divergently selected for abdominal fat. A SNP (G54C) was found in CDS region of chicken MC4R gene. The analysis of the least squares and variance revealed a significant association between the G54C SNP and BW, CW and SL at 7 wk of age, and there were significant differences in different genotypes (p<0.05). The results from protein secondary structure prediction and tertiary structure prediction showed that it appeared a helix in $13^{th}$ amino acid and two strands at $14^{th}$ and $15^{th}$ amino acid in mutant protein, respectively. It maybe induce the change of the activity or function of MC4R gene in poultry.

• Journal of the Korean Magnetic Resonance Society
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• v.14 no.2
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• pp.88-104
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• 2010

Human melanocortin-4 receptor (hMC4R) has a critical role in part of energy homeostasis, and their heterozygous mutations related in genetic cause of severe human obesity. In order to study the structure and function of these membrane proteins, it is important to prepare the samples. However, the preparation of transmembrane peptide is seriously difficult and time-consuming. Overexpression and purification of membrane proteins was reported to be difficult due to their innate insoluble and toxic properties. Among the many difficulties, the most important is the difficulty in obtaining sufficient quantities of purified protein. Recently, we succeed to produce large amounts of the second transmembrane domain from the wild-type hMC4R (wt-TM2) and D90N mutant hMC4R (m-TM2) and proposed the structural difference of them in membrane-like environments. In this paper, we demonstrate the optimization procedures to express and purify wt-TM2 or m-TM2 peptides, and solution NMR studies in different detergents to get high-resolution spectra were also described.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1996.11a
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• pp.153-159
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• 1996

${\alpha}$-Melanotropin (Ac-Ser-Tyr- Ser-Met-Glu$\^$5/-His-Phe-Arg-Trp-Gly$\^$10/-Lys-Pro-Val-NH$_2$) is one of the first peptide hormones to be isolated and have its structure determined. It was early recognized to have essentially the same N-terminal tridecapeptide sequence as adrenocorticotropic hormone (ACTH) except that the N-terminal was acetylated in the case of ${\alpha}$-MSH but not in the case of ACTH, indicating that their biosyntheses were different (Figure 1). Subsequently it was discovered that ${\alpha}$-MSH and ACTH were derived from the same gene, currently referred to as proopiomelanocortin (POMC). Its original bioactivity was pigmentation, but it also was recognized that it may have activity in the central nervous system, though the precise nature of these central activities have been controversial. The recent cloning and expression of five melanocortin receptors, with the MC3 and MC4 receptors found primarily in the brain and the MC5 receptor (MC5-R) found throughout the body, has provided new impetus to understand the structure-activity relationships of ${\alpha}$-MSH at these receptors. The effects of ${\alpha}$-MSH on pigmentation are mediated by the MC1-R expressed specifically on the surface of melanocytes. Similarly the MC2-R is involved in the regulation of adrenal steroidogenesis by ACTH. However, given the complexity of expression of the MC3, MC4, and MC5 receptors, it has not been possible to identify any simple correlations between these receptors and the reported biological activities of the melanocortin peptides. Consequently, potent and receptor specific agonists and especially antagonists would be extremely valuable tools for the determination of the physiological roles of the MC3, MC4, and MC5 receptors. Though the extensive structure-activity relationships have provided much information on agonist activity related to pigmentary effects, only recently has it been possible to begin to systematically develop potent and selective antagonists.