Growth Hormone Receptor Gene Research Articles

POLYMORPHISM OF GROWTH HORMONE RECEPTOR GENE AND MYOGENIC FACTOR 5 GENE IN DAIRY CATTLE POPULATIONS

Investigations of the genetic structure features of the populations of Ukrainian Black-and-White and Red-and-White dairy breeds by polymorphism of growth hormone receptor (GHR) and myogenic factor 5 (MYF5) genes were carried out. AluI-polymorphism in the promoter fragment of the GHR gene and TaqI-polymorphism in the second intron of the MYF5 gene was detected using polymerase chain reaction and restriction analysis (PCR-RFLP). According to the research results, it was shown that the growth hormone receptor and myogenic factor 5 genes in the populations of Ukrainian Black-and-White and Red-and-White dairy breeds are polymorphic. In the population of the Ukrainian Black-and-White dairy breed at the GHR locus, the frequency of the AluI+ allele was 0.61; allele AluI- – 0.39; at the MYF5 locus, the TaqI+ allele frequency was 0.65; allele Taq- – 0.35, respectively. In the population of the Ukrainian Red-and-White dairy breed at the GHR locus, the frequency of the AluI+ allele was 0.54; allele AluI- – 0.46; at the MYF5 locus, the TaqI+ allele frequency was 0.64; allele Taq- – 0.36, respectively. Both experimental populations for GHR and MYF5 loci are in a genetic equilibrium state according to Hardy-Weinberg, which indicates the absence of microevolutionary changes in the process of their reproduction. There were no significant fluctuations in the genetic structure according to the revealed features of the genotype and allele frequencies distribution. The breeding work that is carried out on both populations does not affect marker alleles (which are described in the work), which is reflected in the features of the genetic-population structure of the experimental groups and their equilibrium state. The features of the distribution of individuals with different genotypes by GHR and MYF5 loci in the populations of both breeds make it possible to carry out further studies to determine the relationship between the identified allelic variants of polymorphic loci with parameters of animal productivity.

Association analysis of novel SNPs in exon 10 of the growth hormone receptor gene with growth traits in Indian sheep

The growth hormone receptor (GHR) gene encodes the type I cytokine receptor that helps in joining the growth hormone to this receptor, thus promoting receptor-dimerization, leading to up-regulating growth. The ovine GHR gene located on chromosome 16, which consists of 10 exons and 9 introns, along with untranslated regions on either side, comprise a total size of 178.09 kb. However, earlier reports about polymorphism have mainly dealt with exon 10 which is also a larger fragment of this gene comprising 1102 bp. Hence, this study was carried out to detect polymorphism in exon 10 of the GHR gene and its association with growth traits. Genomic DNA was isolated from blood samples of Madras Red and Mecheri sheep breeds from India. Part of exon 10 (895 bp) of the GHR gene was amplified and sent for sequencing. The sequence analysis revealed transition of nucleotide G>A at loci G177624A and G177878A in both sheep breeds. Populations were screened by Tetra-primer ARMS-PCR. The genotype frequencies of GG, GA and AA were 0.276, 0.519 and 0.205 at 177624 G>A, and 0.307, 0.444 and 0.149 at 177878 G>A in Madras Red sheep; whereas in Mecheri they were 0.476, 0.372 and 0.152 at 177624 G>A, and 0.629, 0.314 and 0.057 at 177878 G>A, respectively. Likewise the estimated allele frequencies of G and A were 0.5355 and 0.4645 at 177624 G>A, and 0.5790 and 0.4210 at 177878 G>A in Madras Red sheep; whereas in Mecheri they were 0.6620 and 0.3380 at 177624 G>A, and 0.7860 and 0.2140 at 177878 G>A, respectively. The effect of sex was significant for birth, six and nine month weight; but non-significant for three and 12 month weight in Mecheri sheep. However, in the Madras Red breed the effect of sex was significant for all body weights except weaning weight. The effect of variations on growth traits, viz., birth weight, weight at weaning, and weight at six, nine and twelve months in both breeds were analysed for their association, and they were found non-significant. Since these SNPs are salient findings of GHR gene polymorphism in Indian sheep breeds, further investigation is required into the significant effects of these novel SNPs, which could be useful for genetic improvement based on marker assisted selection.

Laron Syndrome Research Paves the Way for New Insights in Oncological Investigation.

Laron syndrome (LS) is a rare genetic endocrinopathy that results from mutation of the growth hormone receptor (GH-R) gene and is typically associated with dwarfism and obesity. LS is the best characterized entity under the spectrum of the congenital insulin-like growth factor-1 (IGF1) deficiencies. Epidemiological analyses have shown that LS patients do not develop cancer, whereas heterozygous family members have a cancer prevalence similar to the general population. To identify genes and signaling pathways differentially represented in LS that may help delineate a biochemical and molecular basis for cancer protection, we have recently conducted a genome-wide profiling of LS patients. Studies were based on our collection of Epstein–Barr virus (EBV)-immortalized lymphoblastoid cell lines derived from LS patients, relatives and healthy controls. Bioinformatic analyses identified differences in gene expression in several pathways, including apoptosis, metabolic control, cytokine biology, Jak-STAT and PI3K-AKT signaling, etc. Genes involved in the control of cell cycle, motility, growth and oncogenic transformation are, in general, down-regulated in LS. These genetic events seem to have a major impact on the biological properties of LS cells, including proliferation, apoptosis, response to oxidative stress, etc. Furthermore, genomic analyses allowed us to identify novel IGF1 downstream target genes that have not been previously linked to the IGF1 signaling pathway. In summary, by ‘mining’ genomic data from LS patients, we were able to generate clinically-relevant information in oncology and, potentially, related disciplines.

Laron Syndrome—Possibilities of Diagnoses, Treatment, and Outcome

Background
 Laron syndrome (growth hormone insensitivity) is a rare autosomal recessive condition characterized by severe short stature with postnatal onset usually (1), particular facial features and hypoglycemia in childhood, and type 2 diabetes mellitus, dyslipidemia, metabolic syndrome, and obesity in adulthood (2), caused by growth hormone receptor (GHR) anomalies (insensitivity). It is estimated that there are 350 people with this condition worldwide (3). The growth hormone receptor mutation prevents the stimulating effects of growth hormone, inducing insulin-like growth factor-1 (IGF1) deficiency. Treatment with recombinant IGF1, the only treatment option which can improve final height (4), is not available for all patients. 
 Aim
 Present the clinical outcomes of a Laron syndrome patient untreated and on hormonal substitution treatment.
 Case Report
 A 18-year-old girl with Laron syndrome diagnosed at the age of 2 years and 10 months, based on the clinical feature of severe short stature (height—63 cm; −8.24 SDS, standard deviation score), particular facial features (protruding forehead, saddle nose, large eyes, sparse and thin silky hair, and high-pitched voice), small hands and feet, and sweating and hypotonic episodes, especially in the morning. The endocrine growth axis assessment revealed an elevated growth hormone concentration (>40 ng/mL; 0–8 ng/mL) and very low serum IGF-1 levels ( A L141X) in the 6 exon of the GHR gene. The growth velocity without hormonal substitution was low at 0.23 cm/month (14.5 cm/63 months). After 15 months (between 8 years 1 month and 9 years 4 months) of IGF1 (mecasermin) treatment, the growth velocity increased to 0.53 cm/month, the girl’s height increased from 77.5 cm (−8.55 SDS) to 85.6 cm (−7.94 SDS). After IGF1 treatment discontinuation, height velocity fell to 0.22 cm/month. At the age of 17 years and 2 months, hormone replacement therapy with mecasermin was resumed up to 18 years. The patient also had associated pubertal delay; thelarche started at the age of 15 and progressed slowly. The final height of the patient was 117 cm. In addition, she has developed focal epilepsy, obesity, and depression.
 Conclusions
 Early diagnosis and hormone substitution therapy may reduce the clinical consequences of complications, improving the prognosis.

A common deletion in the growth hormone receptor gene (d3-GHR) in the offspring is related to maternal placental GH levels during pregnancy

BackgroundA common growth hormone receptor polymorphism with deletion of exon 3 (d3-GHR) has previously been linked to increased postnatal growth on the one hand and decreased fetal growth on the other. Regulation of fetal growth is positively dependent on secretion of placental GH (hGH-V). ObjectiveWe explored the effect of the fetal d3-GHR genotype on maternal serum levels of hGH-V and fetal growth. The cellular localization of hGH-V synthesis and the GH receptors were determined in normal placentas. Methods43 healthy mother-child pairs were examined during pregnancy with measurements of hGH-V during third trimester, and serial ultrasound measurements determined fetal growth rate. Birth anthropometrics were obtained. The GHR genotype of the child was analysed postnatally. Immunohistochemical (IHC) analysis was conducted on four placentas. ResultsThe presence of the d3-GHR genotype was associated with a markedly reduced concentration of hGH-V in maternal serum (β −0.52, SE 0.24, p = 0.04) compared to those who had a fl/fl genotype. Accordingly, a tendency towards reduced fetal growth rate during third trimester (β −25.8, SE 12.7, p = 0.05) and a lower birth weight were found among carriers of the d3-GHR allele, but these associations did not reach statistical significance (p = 0.08). IHC analysis showed expression of placental GH and GHR in the villous syncytiotrophoblast, the extravillous trophoblast, and the decidual cells and smooth muscle cells in chorionic vessels. ConclusionsThe presence of the d3-GHR polymorphism in the fetus was associated with lower maternal serum levels of hGH-V, decreased fetal growth rate in third trimester and lower birth weight compared to the wildtype.

Growth hormone receptor knockout: Relevance to xenotransplantation.

Xenotransplantation research has made considerable progress in recent years, largely through the increasing availability of pigs with multiple genetic modifications, effective immunosuppressive therapy, and anti-inflammatory therapy to protect pig tissues from the primate immune and inflammatory responses and correct molecular incompatibilities.Further study is required regarding identification and investigation of physiological incompatibilities. Although the exact cause remains uncertain, we and others have observed relatively rapid growth of kidney xenografts after transplantation into nonhuman primates (NHPs). There has also been some evidence of growth, or at least ventricular hypertrophy, of the pig heart after orthotopic transplantation into NHPs. Rapid growth could be problematic, particularly with regard to the heart within the relatively restricted confines of the chest. It has been suggested that the problem of rapid growth of the pig organ after transplantation could be resolved by growth hormone receptor (GHR) gene knockout in the pig. The GHR, although most well-known for regulating growth, has many other biological functions, including regulating metabolism and controlling physiological processes. Genetically modified GHRKO pigs have recently become available. We provide data on their growth compared to comparable pigs that do not include GHRKO, and we have reviewed the literature regarding the effect of GHRKO, and its relevance to xenotransplantation.

Genetic causes of growth hormone insensitivity beyond GHR.

Growth hormone insensitivity (GHI) syndrome, first described in 1966, is classically associated with monogenic defects in the GH receptor (GHR) gene which result in severe post-natal growth failure as consequences of insulin-like growth factor I (IGF-I) deficiency. Over the years, recognition of other monogenic defects downstream of GHR has greatly expanded understanding of primary causes of GHI and growth retardation, with either IGF-I deficiency or IGF-I insensitivity as clinical outcomes. Mutations in IGF1 and signaling component STAT5B disrupt IGF-I production, while defects in IGFALS and PAPPA2, disrupt transport and release of circulating IGF-I, respectively, affecting bioavailability of the growth-promoting IGF-I. Defects in IGF1R, cognate cell-surface receptor for IGF-I, disrupt not only IGF-I actions, but actions of the related IGF-II peptides. The importance of IGF-II for normal developmental growth is emphasized with recent identification of defects in the maternally imprinted IGF2 gene. Current application of next-generation genomic sequencing has expedited the pace of identifying new molecular defects in known genes or in new genes, thereby expanding the spectrum of GH and IGF insensitivity. This review discusses insights gained and future directions from patient-based molecular and functional studies.

GHR and IGF2R genes may contribute to normal variations in craniofacial dimensions: Insights from an admixed population

This study aimed to determine whether single nucleotide polymorphisms in the growth hormone receptor (GHR) and insulin-like growth factor 2 receptor (IGF2R) genes are associated with different craniofacial phenotypes. A total of 596 orthodontic and 98 orthognathic patients from 4 cities in Brazil were included for analyses. Angular and linear cephalometric measurements were obtained, and phenotype characterizations were performed. Genomic DNA was collected from buccal cells and single nucleotide polymorphisms in GHR (rs2910875, rs2973015, rs1509460) and IGF2R (rs2277071, rs6909681, rs6920141) were genotyped by polymerase chain reactions using TaqMan assay. Genotype-phenotype associations were assessed in the total sample (statistical significance was set at P<8.333×10-3) and by a meta-analytic approach implemented to calculate the single effect size measurement for the different cohorts. Rare homozygotes for the GHR rs2973015 showed increased measurements for the lower anterior facial height (ANS-Me) and mandibular sagittal lengths (Co-Gn and Go-Pg). In contrast, common homozygotes for the IGF2R rs6920141 presented reduced measurements for these dimensions (ANS-Me and Go-Pg). Furthermore, the less common homozygotes for IGF2R rs2277071 had reduced maxillary sagittal length (Ptm'-A'). The meta-analytical approach replicated the associations of rs2973015 with ANS-Me, rs2277071 with Ptm'-A', and rs6920141 with Go-Pg. Our results provide further evidence that GHR contributes to the determination of mandibular morphology. In addition, we report that IGF2R is a possible gene associated with variations in craniofacial dimensions. Applying meta-analytical approaches to genetic variation data originating from likely underpowered samples may provide additional insight regarding genotype and/or phenotype associations.

Functional genes polymorphism associations with egg quality traits in the populations of dual-purpose

Aim. To study the egg quality traits of Poltava Clay chicken line 14 and Rhode-Island Red chicken line 38 with different genotypes of the prolactin gene (PRL), growth hormone gene (GH), growth hormone receptor gene (GHR), insulin-like growth factor I gene (IGF-I) and Mx gene (Mx). Methods. The study was conducted using the method of polymerase chain reaction and restriction fragment length polymorphism analysis (PCR-RFLP). Results. We found signifi cant differences in line 14 for egg quality between prolactin, growth hormone, growth hormone receptor and Mx loci. Homozygous individuals CC and TT by prolactin locus prevailed over heterozygotes CT for egg weight on the 30th week of life. As for the growth hormone gene, the maximum differences for egg weight were revealed when comparing BC heterozygotes with CC homozygotes. As for the growth hormone receptor gene, signifi cant prevalence (p &lt; 0.05) of individuals with the B0 genotype over A0 by parameters of egg yolk weight was noted at the age of 52 weeks. Signifi cant differences (p &lt; 0.05) in eggshell thickness were determined for genotypes AG and GG by Mx gene in week 52. There were signifi cant differences (p &lt; 0.05) in egg quality traits for prolactin and Mx gene for chickens of line 38. TT homozygotes by prolactin locus are characterized by the prevalence of values (p &lt; 0.05) for the egg, yolk and shell weight. In case of Mx gene polymorphism, the heterozygous individuals were characterized by signifi cantly higher values (p &lt; 0.05) of egg and albumen weight on the 30th week of life. There were no signifi cant differences in both experimental chicken lines for other egg quality traits between individuals with different genotypes. Conclusions. The data obtained are recommended for the use in breeding programs for Poltava Clay chicken line 14 and Rhode-Island Red chicken line 38 with the aim of obtaining microlines with the different genotypes for PRL, GH, GHR and Mx loci.

Laron syndrome - A historical perspective.

Laron Syndrome (LS) [OMIm#262500], or primary GH insensitivity, was first described in 1966 in consanguineous Jewish families from Yemen. LS is characterized by a typical phenotype that includes dwarfism, obesity and hypogenitalism. The disease is caused by deletions or mutations of the GH-receptor gene, causing high serum GH and low IGF-I serum levels. We studied 75 patients from childhood to adult age. After early hypoglycemia due to the progressive obesity, patients tend to develop glucose intolerance and diabetes. The treatment is by recombinant IGF-I, which improves the height and restores some of the metabolic parameters. An unexpected finding was that patients homozygous for GH-R defects are protected from malignancy lifelong, not so heterozygotes or double heterozygote subjects. We estimate that there are at least 500 patients worldwide, unfortunately only few treated.

Association between growth hormone receptor gene polymorphism and craniofacial morphology – A review

Craniofacial development is a sophisticated process which has multiple genetic and epigenetic factors involved. Disturbance in the developmental process can cause morphologic and functional defects, which may also affect the psychological health of the individual. It is imperative for orthodontists to have a thorough knowledge about the growth of the face in general and of the maxilla and mandible in particular, to help modify growth and treat the skeletal malocclusions. Multiple genes have been implicated in the growth of the craniofacial complex, growth hormone receptor gene (GHR) being one of them. Growth hormone plays an important role in the post-natal development of an organism, both skeletal and soft tissue growth. Mutation of its receptor will affect the expression of the gene, and in turn influence the growth. Studies have shown that polymorphisms in the GHR gene receptors affect the morphology of the maxillomandibular skeleton. This article is a review about the polymorphisms of the GHR gene which affect the facial skeletal pattern.

Indel variants within the PRL and GHR genes associated with sheep litter size.

Growth hormone and prolactin belong to the class of peptide hormones that have a wide range of regulatory functions. In this study, polymorphisms of growth hormone receptor (GHR) and prolactin (PRL) genes were analysed as candidate genes, which are responsible for the litter size in Australian White (AUW) sheep. According to the statistical analyses results, the polymorphism information content (PIC) values of the PRL-P1-ins-23bp, GHR-P2-del-23bp and GHR-P8-del-23bp were 0.371, 0.366 and 0.375, respectively, which indicates the high genetic polymorphism in AUW sheep. Moreover, all indel loci are not conformed to the HWE (p<.05). Further, our findings revealed that the PRL-P1-ins-23bp polymorphism in the ovine PRL gene was significantly related to the first parity litter size (p=.001) and the DD genotype displaying the highest genotypic mean. Meanwhile, the GHR-P2-del-23bp and GHR-P8-23bp indels in the ovine GHR gene were significantly correlated with first parity litter size (p<.05), and the individuals with the genotype II showed significantly higher litter size than others. Collectively, these results demonstrated that our findings could be useful for future sheep breeding strategies based on the molecular-assisted selection (MAS).

Association of GHR Polymorphisms with Milk Production in Buffaloes.

Simple SummaryThe present study reported two missense mutations in the buffalo GHR gene: A novel (c.380G>A) and (c.836T>A) which was described in previous studies. These two single nucleotide polymorphisms (SNPs) were found to be associated with milk yield, fat %, protein %, and 305 day-milk, fat and protein yield, with higher performance for AA haplotype animals. Therefore, selection of buffaloes with AA haplotype would more likely improve milk production traits. Consequently, this would allow breeders to take more precise selection decisions, leading to significantly higher productivity and profitability within the Egyptian buffalo herds.For its role in the mediation of growth hormone (GH) galactopoietic effect, growth hormone receptor (GHR) was considered a functional candidate gene for milk performance in cattle. However, its genetic variation and potential effect have not been investigated in Egyptian buffaloes. This study aimed to screen GHR for polymorphisms and study their associations with milk traits in Egyptian buffaloes. Polymerase chain reaction, single-strand conformation polymorphism, and sequencing were used to identify mutations in 4 exons (E4–E6 and E8) of the GHR gene in 400 Egyptian buffaloes. No polymorphisms were found in E4, while 2 SNPs (c.380G>A/p.Arg127Lys and c.387C>T/p.Gly129) in E5, one silent mutation (c.435A>G/p.Pro145) in E6, and another missense mutation (c.836T>A/p.Phe279Tyr) in E8 were detected. The c.380G>A SNP in the extracellular domain was associated with milk yield, fat %, protein %, and 305-day milk, fat and protein yield, with higher levels in animals carrying the mutant A allele. The c.836T>A SNP in the transmembrane domain was associated with milk yield, fat %, protein %, and 305-day milk, fat and protein yield, with higher milk yield and lower fat %, protein %, fat and protein yield in the mutant A allele-animals. Interestingly, animals with the two mutant AA alleles produced higher milk yield, fat %, protein %, fat and protein yield, accompanied with upregulated expressions of GHR, GH, insulin-like growth factor 1 (IGF1), prolactin (PRL), prolactin receptor (PRLR), β-casein (encoded by CSN2 gene), and diacylglycerol acyltransferase-1 (DGAT1) genes and proteins in milk somatic cells. Therefore, selection of Egyptian buffaloes with mutant AA haplotypes for the novel c.380G>A SNP and the well-known c.836T>A SNP could improve milk yield and quality in buffaloes.

Detecting novel Indel variants within the GHR gene and their associations with growth traits in Luxi Blackhead sheep

The growth hormone is important in the regulation of metabolism and energy homeostasis and acts through a growth hormone receptor (GHR). In this work, genetic variations within the ovine GHR gene were identified and tested for associations with body morphometric traits in Chinese Luxi Blackhead (LXBH) sheep. Novel deletion loci in the LXBH GHR gene included P2-del-23 bp and P8-del-23 bp indel variants. The polymorphic information content (PIC) was 0.329 in P2-del-23 bp and 0.257 in P8-del-23 bp. Moreover, both indel polymorphisms were not at Hardy-Weinberg equilibrium (p < 0.05) in the LXBH population. Statistical analyses revealed that the P2-del-23 bp and P8-del-23 bp indels were significantly associated (p < 0.05) with several growth traits in rams and ewes, including body weight, body height, chest depth, chest width, chest circumference, cannon circumference, paunch girth and hip width. Among the tested sheep, the body traits of those with genotype DD were superior to those with II and ID genotypes, suggesting that the ‘D’ allele was responsible for the positive effects on growth traits. Thus, these results indicate that the P2-del-23 bp and P8-del-23 bp indel sites and the DD genotype can be useful in marker-assisted selection in sheep.

The Role of Growth Hormone Receptor Isoforms and Their Effects in Bone Metabolism and Skeletal Fragility.

Acromegaly and Growth Hormone Deficiency (GHD) are associated with skeletal fragility and with an increased prevalence of Vertebral Fractures (VFs). In the most recent years, several authors tried to investigate surrogate markers that may predict the risk of bone fragility in these endocrine disorders. The aim of this review is to evaluate the role of GH receptor polymorphisms in skeletal fragility in patients affected by GHD and acromegaly. In fact, until now, two different isoforms of the GH Receptor (GHR) were described, that differ for the presence or the absence of transcription of the exon 3 of the GHR gene. Both the isoforms produce a functioning receptor, but the exon 3-deleted isoforms (d3-GHR) has a higher sensitivity to endogenous and recombinant GH as compared to the full-length isoform (fl-GHR).

Identification of the cDNA Encoding the Growth Hormone Receptor (GHR) and the Regulation of GHR and IGF-I Gene Expression by Nutritional Status in Reeves' Turtle (Chinemys reevesii).

Chinemys reevesii (Reeves’ turtle) is a slow-growing reptile that is distributed widely across China. Prior to this study, the cDNA sequence of the growth hormone receptor (GHR) in the Reeve’s turtle, or how periods of starvation might influence the gene expression of GHR and insulin-like growth factor I (IGF-I) in this species, were unknown. Here, we identified the full-length sequence of the cDNA encoding GHR in Reeves’ turtle by using RT-PCR and RACE. The full-length GHR cDNA was identified to be 3936 base-pairs in length, with a 1848 base-pair open reading frame (ORF) that encodes a 615 amino acid protein. Analysis showed that GHR mRNA was detectable in a wide range of tissues; the highest and lowest levels of expression were detected in the liver and the gonad, respectively. IGF-I was also expressed in a range of tissues, but not in the gonad; the highest levels of IGF-I expression were detected in the liver. After 4 weeks of fasting, the expression levels of GHR and IGF-I in the liver had decreased significantly; however, these gradually returned to normal after refeeding. We report the first cloned cDNA sequence for the GHR gene in the Reeve’s turtle. Our findings provide a foundation from which to investigate the specific function of the GHR in Reeve’s turtle, and serve as a reference for studying the effects of different nutrient levels on GHR expression in this species.

PROFIL GEN RECEPTOR GROWTH HORMONE (rGH) PADA SAPI MADRASIN

Cross-breeding between Madura cattle and exotic breeds (exotic cows) occurs in Madura area. The reality in the field shows that the cross-breeding occurs between Limousin cow and Madura cow and the result of the breeding is called as Madrasin cow. One of factor that influences the animal’s growth is Growth Hormone Receptor (GHR). GHR is needed by Growth Hormone (GH) to carry out its effects on target tissues. The purpose of this study is to identify the profile of Growth Hormone Receptors in Madrasin cow. This research was conducted on farmers in Bangkalan, East Java and the Center of Veterinary, Denpasar in MayJune 2017. This study used 14 cows Madrasin. The samples of this study were blood which were taken and used for analyzing DNA that includes DNA isolation, DNA amplification by using Polymerase Chain Reaction (PCR) and Restriction Fragment Length Polymorphism (RFLP) method to determine the genotype. An identification of Growth Hormone Receptor gene polymorphism is done through digesting the DNA fragment of 298 bp by the restriction enzyme AluI. The results shows that the frequency of Growth Hormone Receptor Gene of cow Madrasin allele A was 0.92 and the G allele was 0.08 with frequency of the A allele is higher than G allele.The genotype changing was found in cow Madrasin as much as 0.85 to 0.14 for the AA and AG. As a result of the study, the researcher concluded that Growth Hormone Receptor gene experienced a changing or polymorphisms in Madrasin cow and information which stated in this study be able to used as a basic for selection.

Impact of the GH‐IGF Axis on Adipose Tissue and Obesity: Are there Benefits of Endocrine Defects

Disruption of the mouse growth hormone receptor gene (GHR−/−) results in dwarf, obese, GH resistant mice that possess low levels of IGF‐1 and high levels of GH with intense insulin sensitivity. These mice are similar to humans with Laron Syndrome (LS) in which the individuals are small in stature with low IGF‐1 and high GH levels. Cancer and diabetes rates in both the GHR−/− mice and LS individuals are low or non‐existent. In this regard, GHR−/− mice have extended longevity, in fact, they are the longest‐lived laboratory mouse. Thus, a defect in the action of GH may be beneficial for increased health‐span and longevity. In attempts to dissect which, if any, of the insulin sensitive tissue contribute to the extended health and lifespan of these mice, we have individually disrupted the GHR gene in liver, muscle, and adipose tissue. Surprisingly, only muscle specific GHR gene disruption resulted in a modest increase in life span while none of the others have the impressive extended longevity seen in GHR−/− mice. Since a decrease in the GH/IGF‐1 axis is important for extended health and lifespan, the ability to down regulate its action in adult life may be beneficial. To that end we have, and are, attempting to disrupt the mouse GHR in adult life. To date, disruption at 6 weeks of age results in female mice with extended longevity. Experiments to ‘knock‐out’ the GHR gene at 6 months and one year are ongoing. Also, since adipose tissue (AT) is metabolically important, data regarding the location and function of AT in these mice will be presented.Support or Funding InformationThis work was and supported by the State of Ohio’s Eminent Scholar Program that includes a gift by Milton and Lawrence Goll, the AMVETS, and NIH R01AG059779.

Digestible lysine effects on gene expression by Japanese quails in the pre-laying phase

This study aimed to determine the effects of digestible lysine levels in the diets of Japanese quail (Coturnix coturnix japonica) on performance, blood parameters and the expression of insulin-like growth factor I, and growth hormone receptor (GHR), apolipoprotein A-I (APOA-I), acetyl-CoA-carboxylase (ACC), and fatty acid synthase (FAS) genes. A total of 288 seven-day-old female Japanese quails were randomly assigned to one of three diets that contained 0.8%, 1.10%, or 1.40% digestible lysine. The birds were slaughtered at 42 days old, and relative gene expression was evaluated in the liver by qRT-PCR using the 2-ΔCT method. Lysine supplementation had no effect on weight gain and feed conversion. Abdominal fat was lower in birds supplemented with 0.8% digestible lysine than those supplemented with 1.10% and 1.40%. Increased total cholesterol and triglycerides were elevated in quails that received supplementation of 1.10% digestible lysine compared with the other diets. High density lipoproteins were decreased in birds that received 0.8% digestible lysine. Quails fed with 1.40% digestible lysine had greater expression of GHR and APOA-I than quails fed diets with 0.8 and 1.10% (P &lt;0.05). The greatest expressions of ACC and FAS were observed in the liver of quails fed with 0.8% digestible lysine. The current results suggest that lysine supplementation in the pre-laying phase allows birds to deposit muscle mass to reach the optimal conformation and body fatness that provides an energetic reserve for the productive phase by modulating the expression of genes related to growth and lipid metabolism.&#x0D; Keywords: Coturnix coturnix japonica, growth, growth hormone, lipid synthesis, lipid metabolism

GH and GHR gene cloning, expression and their associations with growth-related traits of the barbel chub (Squaliobarbus curriculus).

Growth hormone (ScGH) and growth hormone receptor (ScGHR) genes from the barbel chub (Squaliobarbus curriculus), in addition to their cDNAs, were cloned. The associations between their mRNA expression levels and growth-related traits were analysed, and the differences in the levels of expression of growth regulation-related genes between the largest and smallest individuals were compared. The full-length 1182-bp cDNA of ScGH contained a 633-bp open reading frame (ORF), and the length of the gene had 2492bp. The full-length 2825-bp cDNA of ScGHRa contained a 1818-bp ORF, and the gene had 6970bp. The full-length 2822-bp cDNA of ScGHRb contained a 1737-bp ORF, and the gene had 8149bp. Quantitative real-time PCR revealed that ScGH was only expressed in the pituitary. ScGHRa was expressed predominantly in muscle, and the expression level of ScGHRb was the highest in the liver. The ScGHRa mRNA levels in the muscle were significantly negatively correlated with the caudal peduncle length. However, no correlation between growth-related traits and ScGH and ScGHRb expression levels were found. Pituitary ScGH, liver GHRb and liver insulin-like growth factor I (igf-1) expression levels were significantly higher in the largest individuals than those in the smallest S. curriculus individuals. Contrarily, the largest individuals had significantly lower expression levels of muscle igf-1 and liver myog than the smallest individuals. Overall, our results provide novel molecular information for growth-regulation study of S. curriculus.