Background: Metabolic impacts of two important alleles of the growth hormone receptors (GHR), one with retention of exon 3 [exon 3 (+) GHR] and the other with the deletion of it [exon 3 (-) GHR], on the metabolic risk factors of type 2 diabetes mellitus (T2DM) are really unknown. We aimed to evaluate relationships between the genotypes and metabolic risk factors of T2DM.Methods: In the present study, 40 patients in pre-diabetic state and 40 healthy subjects were selected based on their clinical and laboratory evidence. For genotyping, DNA was extracted from the leukocytes of peripheral blood and amplified by multiplex polymerase chain reaction method.Genotypes of the amplified DNA samples were resolved using 1.5% agarose gel electrophoresis.Other risk factors were also determined by using standard methods and appropriate kits.Findings: Frequency of the homozygote exon 3 retained genotype [exon 3 (+/+) GHR] was significantly higher in the subject in pre-diabetic state (P<0.001); the frequency of exon 3 (+/-) GHR and exon 3 (-/-) GHR genotypes were significantly higher in the control subjects (P<0.001). The decrease of metabolic risk factors was profound in subjects with exon 3 (-/-) GHR genotype (P<0.001).Conclusion: The presence of exon 3 deleted allele of GHR, especially in the homozygosity situation, was associated with decreased levels of the metabolic risk factors of type 2 diabetes mellitus. So, the exon 3 deleted GHR may have more robust biological and metabolic activities lead to the resistance against T2DM.

Growth hormone (GH) is a single polypeptide hormone which is produced and secreted by cells of the anterior pituitary gland. This hormone exerts diverse growth promoting and metabolic effects. As GH circulates in the blood, it binds to GH receptors (GHR), a trans membrane protein expressed on the surface of liver, adipose, kidney, heart, intestine, lung and muscle cells. After receptor binding, GH induces GHR dimerization and JAK2 is activated after its association with a dimerized GHR. A growth hormone antagonist (GHA) was produced in E.coli by a mutation that would block GH by preventing the GHR dimerization. In this study, we evaluated the effect of mutagenesis on binding energy of GH and GHA to their related receptor. The growth hormone and its mutant 3D structures were obtained from PDB (http://www.rcsb.org/pdb/home) and M4T server, respectively. Likewise, GHR conformational structure, was found in NCBI (http://www.ncbi.nlm.nih.gov). GH and GHA affinity for binding to GHR was analyzed by HEX docking software and energy total (E total) was obtained. GH and GHA E total were -648.13 and -698.68 respectively. This data demonstrates that GHA affinity for binding to GHR is higher than GH affinity. So GHA in completion to GH will overcome GH in binding to GHR, it can act as an antagonist to prevent excessive growth and cure acromegaly, diabetes and cancer.

This investigation aimed to study polymorphism of growth hormone (GH), growth hormone receptor (GHR), and insulin like growth factor 1 (IGF-1) genes and their associations with growth and carcass traits in Mazandaran native chicken.200 male chicks were reared and slaughtered at 12 weeks of age. Traits including live weight at 4, 8 and 12 weeks of age, body weight and weights of heart, liver, gizzard, spleen, and abdominal fat, pH of meat, water holding capacity of the meat and intramuscular fat were recorded. Before dissecting birds, blood samples were collected and DNA was extracted. The frequency of alleles (+and -) were determined to be 0.627 and 0.373 for GH locus, 0.715 and 0.285 for GHR locus, and 0.407 and 0.593 for IGF-1 gene locus, respectively. Hardy-Weinberg equilibrium study using Chi-square test showed that the studied population was not in Hardy-Weinberg equilibrium. Analysis of phenotypic and genotypic data showed a significant association between genotypes of GH gene and live weights at 8 and 12 weeks of age and carcass weight. Significant associations were found between the GHR gene with live weight at 12 weeks of age and carcass weight and also between IGF-1 gene with abdominal fat and intramuscular fat (P<0.05). Generally, it can be concluded that GH, GHR and IGF-1 genes can be used as candidate genes for improving growth and carcass traits in Mazandaran native fowls.

In the present study the allelic polymorphisms of GH, GHR and TGFb3 genes and its association with egg production traits were investigated. Blood samples randomly were collected from breeder hens of Mazandaran native fowls breeding station and transported to the laboratory in cold chain condition. DNA was extracted using modified salting out method and the desired loci were amplified by specific primers. All samples genotyping were carried out by RFLP-PCR method. The frequency of each (+) and (-) alleles was estimated at 0.7981 and 0.2019 for GH, 0.9937 and 0.0063 for GHR and 0.8037 and 0.1961 for TGFb3 loci, respectively. The heterozygote genotype was detected in both GH and TGFb3 loci but all individuals showed homozygote genotype in GHR marker site. The chi-squared test showed that all individuals in both GH and TGFb3 loci were in HW equilibrium. Statistical analysis of showed that GH marker site had a significant effect on both phenotypic and breeding values of egg weight at puberty (EWM) and age at first laying egg (AFE), respectively.The mean comparison showed that individuals with -/- genotype in GH marker site had higher phenotypic values for EWM but lower breeding values for AFE trait. The GHR and TGFb3 loci and also the interaction between GH×TGFb3 loci were not statistically significant on phenotypic and breeding values of mentioned traits.

The chicken growth hormone gene is considered as one of the most important candidate genes that can influence chicken performance traits because of its crucial function in growth and metabolism. In order to detect polymorphism in GH and GHR loci 160 blood samples were collected randomly from breeder hens of Mazandaran native fowls breeding station. DNA was extracted using modified salting out procedures and polymerase chain reaction (PCR) were used for amplification of fragments with the length of 1050 bp at GH and 718 bp at GHR loci. The treatment of fragments at GH and GHR loci with SacI and HindIII restriction enzymes were revealed+, - and A and B alleles, respectively. The frequencies of alleles at GH locus were + (0.7981), - (0.2019) and for GHR were A (0.9937) and B (0.0063). The genotype frequencies were +/+ (0.6153), +/- (0.3653) and -/- (0.0192) for GH locus and AA (0.9937) and BB (0.0063) for GHR locus. Low heterozigosity of GH gene could be due to closed and small effective number size of flock. Phenotypic analysis showed that GH genotypes were significantly affected body weight (BW) at 12 weeks of age (P£0.03). Comparison of means indicated that+/+genotypes had higher BW at 12 weeks than the other genotypes. The relationships between GHR and other GH genotypes with phenotypic data or breeding values traits were not significant (P>0.05).

The functional role of the exon 3 growth hormone receptor (d3GHR) polymorphism in human and its distributions in different populations is not clearly understood. The presence of full length growth hormone (flGHR) is the most important in metabolic risk factors. The aim of this study was to define the frequency distribution of d3GHR/full-length GHR in an Iranian population. The presence of the d3GHR polymorphism in healthy volunteers blood DNA (n=80, male=30 and female=50) was assessed by PCR using specific primers. The 935-bp and 592-bp fragments indicate the presence of the flGHR and the exon3 deletion of GHR, respectively. The distribution of the GHR genotypes in this study were 31.4% (n=24) for fl/flGHR, 49.7 % (n=41) for fl/d3GHR, and 19.0 % (n=15) for d3/d3GHR. Frequencies of fl allele and d3 allele were 55.4% and 44.4% within whole population, respectively. There was no difference in allels frequencies of GHR in male (fl=0.583, d3=0.417) and female (fl=0.540, d3=0.460) when compared with whole population.The results showed that the frequency of d3/d3GHR isoform was significantly lower than that of the fl/flGHR and d3/flGHR. The frequencies of GHR polymorphisms were likely consistent with previous reports. Our finding is also consistant with Mexican population. The advantage of existence of the d3/d3 rather than fl/flGHR polymorphisms in individuals and in correlation with diseases opens new insights for GH and insilin-like-growth factor-1 (IGF-I) axis.

The growth hormone (GH) gene is a candidate for growth trait in farm animals and plays an important role in growth metabolism. Growth hormone can contribute in growth metabolism when it's receptor (GHR) are on cells target. The single nucleotide polymorphism was occurred in GH and GHR genes and that associated with carcass traits in Lori-Bakhtiari sheep breed with using PCR-SSCP. In this research, blood samples were collected from the left jugular vein from 152 Lori-Bakhtiari sheep breed. Genomic DNA was extracted from blood samples by using the salting-out procedure and PCR were used to amplify the regions are located in exon 4 (214 bp segments) of the ovine GH gene and exon 10 (218 bp segments) of the ovine GHR Gene. The single stranded conformation polymorphism (SSCP) patterns of PCR products were studied using acrylamide gel electrophoresis and silver-nitrate staining method. The result showed polymorphism in GH gene but any difference between banding patterns for GHR gene was not observed. The sequencing results showed the presence of 5 Single nucleotide polymorphism for GH gene in the studied population. No significant associations of the available genotypes in the exon 4 of the ovine GH Gene with carcass traits.

The growth hormone receptor (GHR) is a cell surface receptor for growth hormone (GH) that is required for GH to carry out its effects on target tissues. Therefore, the aim of this study was to identify and analysis of SNPs in the promoter region of GHR gene in Iranian local cattle breed (Bos taurus). The part of promoter region of GHR gene was screened by single strand conformation polymorphism (SSCP) method and DNA sequencing. A total of 3 distinct SSCP patterns were observed which further revealed an A/G transition at position - 154 and two length of TG microsatellite (11 and 17 TG repeats) upon sequence analysis in amplified fragment. The genotype frequencies of AA (TG17/17), G (TG11/11) and GA (TG17/11) were 0.34, 0.24 and 0.52 respectively. In silico analysis has been shown that the single nucleotide polymorphism (SNP) at position -154 is very close to the putative binding site for C/EBP transcription factor. The possible functional activity of identified genetic variation should be approved using gene expression analysis.