Growth Hormone Receptor Gene Research Articles

Association of alcohol with lung cancer risk in men with different growth hormone receptor genotypes

ObjectiveTo test whether genetic variants of the growth hormone receptor gene (GHR) modulate the effect of lifestyle variables on lung cancer (LC) risk. Materials and methodsThis population-based cohort study involved 6,439 men from the Japan-Hawaii Cancer study drawn from the Kuakini Honolulu Heart Program who were cancer-free at baseline examination (1965–1968; age 45–68 years) and followed-up until December 1999. We determined the association of GHR SNP rs4130113 genotypes GHR-AA (common allele A homozygotes) and GHR-G (minor allele G carriage) with alcohol drinking, BMI, physical activity and cigarette smoking in relation to LC and non-small cell LC (NSCLC). Results were expressed as hazard ratios and 95 % CIs estimated from Cox proportional hazard models. ResultsOver mean 26.7 ± 7.4 SD years follow-up, 190 LC cases, including 133 NSCLC cases, were diagnosed. After adjusting for age, education, alcohol intake, BMI, physical activity, cigarette smoking, green tea consumption and dietary saturated fat, main-effect Cox models showed that compared with GHR-AA, GHR-G was associated with protection against LC: HR = 0.75 (95 % CI, 0.56–1.00). Full Cox models showed GHR-G interacted with alcohol intake only (β = 1.171; p = 0.0003; drinks per week: β = 0.279; P = 0.0025). Stratified analyses showed that for GHR-AA, drinkers had reduced LC risk (HR = 0.53; 95 % CI, 0.34–0.84), and that <2 drinks/week had the strongest protection (HR = 0.39; 95 % CI, 0.18–0.84). In contrast, for GHR-G, alcohol drinkers had increased LC risk (HR = 1.74; 95 % CI, 1.11–2.75) which was dose-dependent (P for trend = 0.003). Results for NSCLC were similar. ConclusionIn men with the GHR-AA genotype, alcohol drinking at a low dose poses significantly less risk of LC compared with non-drinkers and higher alcohol consumption., the overall relationship being U-shaped. In contrast, in GHR minor allele carriers, alcohol posed a progressively greater risk of LC as amount consumed increased

The Pattern of Gene Expression (Igf Family, Muscle Growth Regulatory Factors, and Osteogenesis-Related Genes) Involved in the Growth of Skeletal Muscle in Pikeperch (Sander lucioperca) During Ontogenesis.

The pikeperch (Sander lucioperca) is an economically important freshwater fish and a valuable food with high market acceptance. It is undergoing important changes in growth and regulatory metabolism during the ontogeny. Hence, the current study aims to investigate the mRNA expression of the growth hormone (gh)/insulin-like growth factor (igf) axis (ghr, igfI, igfbp, igfr), muscle regulatory factors (pax7, myf5, myod, myogenin, mrf, mymk, mstn), and osteogenesis-related genes (colla1a, fib1a, on, op, ostn) from hatching through day 40th post-hatching (DPH). The average total length (TL) of larvae measured at hatching was 3.6 ± 0.4 mm (67 degree days), and at the end of the experiment (40 DPH, 777 degree days), it was 27.1 ± 1.1 mm. The results showed three phases of gene expression in day 0 (egg), larval, and juvenile stages of pikeperch, which can be a progression or transition from the initial state toward the juvenile state. The expression pattern of myf5, mymk, and fib1a genes showed the highest value at day 0. The growth hormone receptor gene (ghr) and igfbp5 were raised to 1 DPH, whereas increased expression of igfI, igfII, igf1bp4, igf1rb, myod2, and mrf4 was detected at 14 DPH. The myod1, pax7, op, ostc, on, igf1ra, and col1a1a genes were highly expressed at 21 DPH and juvenile stages. According to the PLS-DA model, the most relevant VIPs are myf5 and mymk as best markers of earlier stages and igf1ra, ostc, pax7, and ghr as markers of later stages of ontogeny. Results from this study suggest that basal metabolism, growth of body cells and muscles, and bone proliferation and development can be regulated by the dynamic changes in gene expression patterns in this species. The identified genes will help to understand the basic biological process of pikeperch larvae and development, which is very important in pikeperch farming.

ASSOCIATION OF GROWTH HORMONE RECEPTOR (GHR) GENE POLYMORPHISMS WITH BODY WEIGHT OF RABBITS: A SYSTEMATIC REVIEW AND META-ANALYSIS

The growth hormone receptor (GHR) gene plays a key role in regulating growth and metabolism. However, the relationship between polymorphic variants of this gene and the body weight of rabbits under different genetic models has not been established. Thus, the objective of this study was to evaluate relationship between GHR gene polymorphisms and body weight of rabbits. Relevant literatures were systematically reviewed using the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guideline. 248 studies were identified and screened against pre-determined inclusion criteria and data were extracted from 17 studies. Each study was subjected to Hardy-Weinberg Equilibrium (HWE) test and six genetic models consisting of co-dominant, dominant, recessive and over-dominant models were fitted using OpenMeta® Analyst Software. The Cohen’s d method was used to calculate standardized mean differences (SMDs) to estimate individual study effect size as well as the overall effect size. Heterogeneity measures were inferred from the Q statistic (based on Chi-square test) and its associated p-value, Tau-squared (τ2), H-squared (H2) and I-squared (I2) values. Publication bias was assessed by Egger’s regression asymmetry test and sensitivity analysis was conducted to detect if the overall effect size was largely due to a single study effect size. There was significant association (P&lt;0.05) of GHR gene with body weight of rabbits under one of the co-dominant models (CG vs GG). However, this association was not significant (P&gt;0.05) under all other genetic models. Further, the results indicated that, cumulatively for all studies included in the meta-analysis of association of GHR gene with body weight of rabbits, GG genotype had higher body weight than CG genotype. However, there was no difference (P&gt;0.05) between CC and CG and CC and GG genotypes. These findings implied that the impact of GHR gene polymorphisms on body weight in rabbits may be influenced by specific genetic models.

The Role of the GH Receptor Polymorphisms as a Prognostic Factor of Vertebral Fractures in Acromegalic Patients Resistant to First-generation SSAs and Treated with Pegvisomant or Pasireotide LAR.

Acromegaly is associated with skeletal fragility and increased prevalence of vertebral fractures (VF). Two isoforms of GH receptor (GHR) have been described, which differ in the presence or absence of a transcript of exon 3 of the GHR gene. Both isoforms produce a functional receptor, but the exon 3-deleted isoforms (d3-GHR) have greater sensitivity to endogenous and recombinant GH than the full-length isoform (fl-GHR). We conducted a longitudinal, retrospective, observational, single-center study to investigate the role of GHR polymorphism as a prognostic factor of incidental VF (I-VF) in firstgeneration somatostatin analogs (fg-SSAs)-resistant acromegalic patients and treated with Pegvisomant or Pasireotide LAR. Seventy-two patients with active acromegaly were included: 28 patients carried the d3-GHR isoform, and 44 patients carried the fl-GHR isoform. Forty-six patients were treated with Pegvisomant in combination with fg-SSAs, and 26 were treated with Pasireotide LAR. At the last follow-up, 58 patients achieved biochemical control of acromegaly. Eighteen patients carried prevalent VF (P-VFs), while 14 patients experienced the occurrence of I-VFs. From the group treated with Pegvisomant in combination with fg-SSAs, 32 patients carried the fl-GHR isoform, and 14 carried the d3-GHR isoform. From the group treated with Pasireotide LAR, 12 patients had the fl-GHR isoform, and 14 patients carried the d3-GHR isoform. I-VF occurred more frequently in patients with the fl-GHR isoform compared to d3-GHR (p =0.04); otherwise, I-VF occurred more frequently in patients with the d3-GHR isoform than fl-GHR (p =0.01). The GHR polymorphisms could improve the therapeutic approach in acromegaly, tailored to the individual patient, in the context of personalized medicine.

Genetic correlations in rabbit growth traits: Insights into the growth hormone receptor gene across diverse strains

Genetic correlations in rabbit growth traits: Insights into the growth hormone receptor gene across diverse strains

Effects of inclusion of the blend of essential oils, organic acids, curcumin, tannins, vitamin E, and zinc in the maternal diet, and of incubation temperature on early and late development of quail

The maternal diet and egg incubation temperature are some of the factors that can influence the embryonic development and performance of the newly chicks at 15 d of age. This study evaluated the effects of adding a blend of organic acids, essential oils, curcumin, tannins, vitamin E, and zinc microencapsulated in to the diet of female quails (Coturnix coturnix japonica) on their productive, reproductive performance and redox parameters of their eggs and the interaction of maternal diet × incubation temperature on embryo (E16 and E18) and chicks development. At 98 d of age, 64 female quails with a mean body weight of 150 g ± 0.5 were distributed into two treatments: a Basal diet or a diet supplemented with blend (Sannimix). The eggs from each female were incubated at 37.5°C (Control) and 38.5°C (High Temperature) throughout the incubation period. After hatching, chicks were distributed in a 2 (maternal diet) × 2 (incubation temperature) factorial design. Female quails supplemented with Sannimix showed better productive and reproductive performance and produced higher-quality embryos. Their offspring had greater weight at hatch and at 15 d of age. The eggs and offspring of supplemented with Sannimix female quails showed better oxidative stability. At E16 and E18, High Temperature increased yolk sac utilization and gene expression of the growth hormone receptor (GHR). At E16, embryos from supplemented with Sannimix female quail had higher expression of insulin-like growth factor type I (IGFI) and heat shock protein 70 kDa genes. At 15 d of age, highest expression of the GHR and IGFI genes was observed in chicks from female quails fed the Sannimix diet, regardless of incubation temperature. Regarding the maternal diet × incubation temperature an improved result was observed for chicks from female quails fed with Sannimix even when eggs are exposed to High Temperature during the incubation. The supplementation of quail diets with blend Sannimix improves productive and reproductive performance, egg quality and their embryos, as well as their offspring quality.

Xenotransplantation of solid organs

Transplantation of genetically modified porcine hearts and kidneys could become asolution to the persistent shortage of human organ donors. Progress has been made in genetic engineering of donor pigs, preservation techniques after organ harvesting and immunosuppression using co-stimulation blockade with anti-CD40/CD40L monoclonal antibodies. Progress has also been made in in the development of methods that detect pathogenic porcine viruses and prevent their transmission to the recipient. As normal land breed pig organs continue to grow in the recipient to their original size, different pig breeds (such as Auckland Island pigs) are now used which reach a final size suitable for humans. Alternatively, aknock-out of the growth hormone receptor gene has been established, e.g., in the 10GM genetically modified pigs from Revivicor/United Therapeutics, USA. The first clinical pilot studies including patients suffering from terminal heart failure are expected to start in Germany in about 2years.

Comparison of ICSI, IVF, and in vivo derived embryos to produce CRISPR-Cas9 gene-edited pigs for xenotransplantation

Genome editing in pigs for xenotransplantation has seen significant advances in recent years. This study compared three methodologies to generate gene-edited embryos, including co-injection of sperm together with the CRISPR-Cas9 system into oocytes, named ICSI-MGE (mediated gene editing); microinjection of CRISPR-Cas9 components into oocytes followed by in vitro fertilization (IVF), and microinjection of in vivo fertilized zygotes with the CRISPR-Cas9 system. Our goal was to knock-out (KO) porcine genes involved in the biosynthesis of xenoantigens responsible for the hyperacute rejection of interspecific xenografts, namely GGTA1, CMAH, and β4GalNT2. Additionally, we attempted to KO the growth hormone receptor (GHR) gene with the aim of limiting the growth of porcine organs to a size that is physiologically suitable for human transplantation. Embryo development, pregnancy, and gene editing rates were evaluated. We found an efficient mutation of the GGTA1 gene following ICSI-MGE, comparable to the results obtained through the microinjection of oocytes followed by IVF. ICSI-MGE also showed higher rates of biallelic mutations compared to the other techniques. Five healthy piglets were born from in vivo-derived embryos, all of them exhibiting biallelic mutations in the GGTA1 gene, with three displaying mutations in the GHR gene. No mutations were observed in the CMAH and β4GalNT2 genes. In conclusion, in vitro methodologies showed high rates of gene-edited embryos. Specifically, ICSI-MGE proved to be an efficient technique for obtaining homozygous biallelic mutated embryos. Lastly, only live births were obtained from in vivo-derived embryos showing efficient multiple gene editing for GGTA1 and GHR.

Identification of genetic variants of bGH, GHR and IGF1 gene and their association with lactation persistency in Tharparkar cattle

Persistency can be explained as number of days during which the high level of milk production is maintained after the peak milk yield. The aim of this study was to identify genetic variants of bovine-Growth Hormone (bGH), Growth Hormone Receptor (GHR) and Insulin like Growth Factor1 (IGF1) gene and their association with lactation persistency in Tharparkar cattle. Study was carried out using data of daily milk yield, monthly test days, total milk yield and peak yield of 372 lactation records of 190 Tharparkar cattle maintained at Livestock Research Centre of ICAR-National Dairy Research Institute from 1996-2019. Lactation persistency was estimated using Woods and Wilminks method and its least squares means were 2.37±0.08 and -5.4±0.56, respectively. Investigations on polymorphism were performed using seven reported primers for amplifying targeted regions of bGH, GHR and IGF1 gene. In PCR-RFLP, bGH-MspI RFLP had shown polymorphism in intron 3 and its genotypic frequencies were TT 0.49, CT 0.39 and CC 0.12. The allelic frequency of C and T were 0.31 and 0.69, respectively. The bGH-AluI RFLP had shown monomorphism in exon 5. GHR-AluI had shown polymorphism in exon 10 with only two genotypes AA and AG with frequency of 0.92 and 0.08, respectively. The frequency of A and G allele was 0.96 and 0.04, respectively. In GHR-StuI and IGF1-TasI in promoter region, RsaI in exon 3 and SnaB I in exon 1 had shown monomorphism. No significant association was found between genetic variants of bGH and GHR with lactation persistency in Tharparkar cattle.

Role of the Growth Hormone Receptor (GHR) Gene in Skeletal Class II Malocclusion and Its Significant Influence on the Skeletal Facial Profile in Both the Sagittal and Vertical Dimensions: A Systematic Review.

This systematic review aims to determine the role of the growth hormone receptor (GHR) gene in skeletal malocclusion and its significant influence on the growth of the maxilla and the mandible in both sagittal and vertical dimensions. A search of the electronic databases of PubMed, Google Scholar, and Cochrane up to and including the year 2023 was made. In addition to this, a hand search of orthodontic and dentofacial orthopaedic journals was carried out. This search included randomized control trials. The Mesh terms used were "skeletal class II malocclusion", "mandibular retrognathism", "sagittal malocclusion", "genetic expression", "genetic factors", "genetic study", "genetic polymorphism", and "single nucleotide polymorphism". The inclusion criteria included studies such as clinical trials and orthopaedic appliances in the presurgical phase. The exclusion criteria for the study were studies not in the English language, case reports, case series, and studies with irrelevant data. It has been cited in various literature that polymorphic variations of the GHR gene could cause variations in mandibular morphogenesis affecting both the mandibular body length and ramal height. However, its effects are quite variable and are based on different population groups. Polymorphism of the GHR gene can be considered a reliable indicator predicting variations in affecting the growth of the mandible with greater significance in affecting the vertical ramal height compared to the body length of the mandible. Its effects on the maxillary skeletal base are rather limited comparatively.

Prevalence of growth hormone receptor gene polymorphisms and their association with milk production and fertility-related traits of cross-bred dairy cows in Sri Lanka

This study investigated the association of selected growth hormone receptor (GHR) gene SNPs with selected fertility and milk production-related phenotypes of cross-bred dairy cows (n = 153) reared on three National Livestock Development Board farms in Sri Lanka. Selected cows were genetically screened for SNPs in the exon 08 (n = 153) and 5’ upstream (n = 118) regions of the GHR gene using the target sequencing method. The relationships between different genotypes and fertility traits (average calving interval, average number of services per conception, and age at first calving) and milk production-related traits (average total lactation yield, average lactation length, and average milk yield) were analyzed using the General Linear Model in SPSS. Among the identified Four GHR SNPs, rs1099014416 was significantly associated with average calving interval and age at first calving. Cows with GG genotype exhibited younger age at first calving (918.51 ± 113.42 days) and longer calving intervals (543.41 ± 43.29 days) compared to cows with GT (1275.18 ± 38.31, 515.09 ± 24.49 days) and TT (1212.89 ± 88.22, 364.52 ± 54.01 days) genotypes. Other SNPs did not show associations with the studied traits. SNP rs109014416 has the potential to be used as a genetic marker for fertility-related traits in the selection of cross-bred dairy cows in Sri Lanka which should be validated with a larger population.

Evaluation of potential genetic marker for growth and carcass traits in Sumba Ongole (Bos indicus) cattle

Objective: This study was conducted to investigate the variants of the growth hormone receptor (GHR), growth hormone-releasing hormone (GHRH), pituitary-specific transcription factor-1 (PIT1), and signal transducer and activator of transcription 5A (STAT5) genes and their effect on growth performance and dressing percentage (DP) parameters. Materials and Methods: A total of 401 DNA samples from Sumba Ongole (SO) cattle were utilized for the polymerase chain reaction-restriction fragment length polymorphism method, of which 200 samples were used for the study of DP association and 74 samples were used to investigate growth performance. The SO cattle growth performance includes the following: birth weight, weaning weight at 205 days of age, weaning average daily gain (ADG), yearling weight at 365 days of age, and post-weaning ADG. Results: The GHR, GHRH, PIT1, and STAT5A genes showed polymorphism. The highest polymorphism information content value was shown in the STAT5A gene. The highest DP value was found in the SO cattle population with the CC genotype (STAT5A), and the lowest DP value was found in the SO cattle population with the GG genotype (GHR). The GHR and STAT5A genotypes were highly associated (p &lt; 0.05) with the DP parameter. Based on locus combination analysis, the highest DP value was found in the SO cattle population with AG|CC genotype (GHR|STAT5A) (57.85%), AG|BB|CC genotype (GHR|GHRH|STAT5A) (57.85%), and AA|BB|BB|CC genotype 18 (GHR|GHRH|PIT1|STAT5A) (56.02%). Conclusion: All investigated genes in this study were polymorphic but were not associated with several growth parameters. The GHR and STAT5A genes can be proposed as genetic markers for the high DP trait in SO cattle in Indonesia, especially the AA genotype (GHR) and CC genotype (STAT5A).

Pırlak Koyun Irkında Bir Batında Doğan Yavru Sayısı ile Ilişkili PRL ve BHR Genlerindeki inDel Varyasyonlar

Numerous molecular genotyping methods are available to analyse local livestock populations at molecular level in which traditional Polymerase Chain Reaction (PCR) guided by specific oligonucleotides is a fast and cost-effective method to investigate single genes. Until today, many genes which are of major effects on litter size have been reported in sheep. Genetic variations in these genes shaping the expression profile at DNA level may lead to differences in litter size among the sheep breeds. This is the first attempt to investigate insertion/deletion (inDel) variations in Prolactin (PRL) intron 2 and Growth Hormone Receptor (GHR) intron 3 and intron 4 genes in Pirlak sheep breed via traditional PCR technique. A total of 100 unrelated animals sampled from representative herds reared in Antalya were genotyped based on absence/presence of 23 base pairs (bp) length inDel in which three genotypes (II, ID, and DD) were detected in all loci. I and D allele frequency were 0.421 and 0.579, respectively in terms of PRL-intron 2 locus. I / D allele frequencies were found as 0.599 / 0.401 and 0.372 / 0.628 in GHR intron 3 and intron 4, respectively. The lowest II (0.181) and DD (0.177) genotype frequencies were detected in GHR-intron 4 and GHR-intron 3 loci, respectively. The lowest (0.177 for DD) and highest (0.448 for ID) genotype frequencies were detected in GHR intron 3 locus across the population. Significant deviation from Hardy-Weinberg Equilibrium (HWE) was detected only in PRL-intron 2 locus. The results of the present study confirm that Pirlak breed conserves sufficient genetic variation in PRL and GHR gene regions which could be utilized in selection strategies in order to increase litter size in the future.

Impact of growth hormone receptor gene on measurements of dimen-sions and body weights of local Iraqi sheep

This research involved a sample of 50 local Iraqi sheep, consisting of 27 males and 23 females, aged between 5 and 17 months. Data collection occurred during two distinct seasonal periods: October 2022 and January 2023. The primary objective was to investigate the variations in the expression of the growth hormone receptor (GHR) and its influence on the physical attributes of local Iraqi sheep within this age range. The results showed that the GHR gene exhibited a marked increase in expression during the second seasonal timeframe with levels of 23.8 ± 0.2 and 29.7 ±1.4 for first period. This increase in gene expression was paralleled by substantial differences in the sheep's body weights, with values of 33.7376±0.732(kg) for the first seasonal period and 35.77±1.111(kg) for the second seasonal period. Similarly, the dressing percentage showed significant differences, with values of 47.71±0.49 (kg) for the first period and 50.11±0.59 (kg) for the second period. Furthermore, carcass weight demonstrated highly statistically significant variations, measuring 16.037±0.440 (kg) during the first seasonal period and 17.978±0.655 (kg) during the second seasonal period. Gender-based analyses revealed significant disparities, with males exhibiting greater weight measurements (kg) (36.764±1.002) compared to females (32.122±806.0). The same trend was observed in carcass weight (18.362±0.606 for males and 15.242±0.369 for females), dressing percentage (49.8±0.0062 for males and 47.8±0.0047 for females), and viscera weight (1.382±0.029 for males and 1.258±0.032 for females). In addition to these findings, body dimension measurements (cm) showed significant differences in lump height, with measurements of 67.81±0.891 in the first period and 64.88±0.717 in the second period. However, non-significant differences were observed in other body dimension measurements. These findings have implications for understanding the genetic factors affecting the growth and development of sheep which can inform breeding and livestock management practices.

Effects of exposing Japanese quail eggs to a low dose of gamma radiation and in ovo feeding by two sources of trace elements on embryonic development activities

The present study investigated the influence of exposing quail eggs to low-dose gamma radiation (GR) and in ovo feeding with 2 sources of a mixture of trace elements (Zn, Fe, and Cu), including sulfate (TES) and loaded with montmorillonite (TEM), on embryonic development activities and prehatch quality. A total of 960 eggs on the seventh day of incubation were randomly divided into 6 groups (160 eggs/group) with 4 replicate of 40 eggs in each. A 3 × 2 factorial arrangement experiment was performed and included 3 sources in ovo feeding with a mixture of trace elements (Zn, Fe, and Cu), including 0 mg/egg, 50 mg TES/egg, and 50 mg TEM/egg with egg irradiation using 0 and 0.2 Gy from GR. Eggs injected with 50 mg TEM/egg and exposed to 0.2 Gy from GR (TEM/GR) was significantly (P ≤ 0.05 and 0.01) higher in hatchability, hatch body weight, and relative organ weight (liver, gizzard, proventriculus, heart, and intestine). The obtained results indicated significant (P ≤ 0.05) decreased in the serum concentration of malondialdehyde (MDA) in TEM/GR group. There was significant (P ≤ 0.05) increased of catalase (CAT) activity and the concentrations of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) in TEM/GR group; however; total antioxidant capacity (T-AOC) was significant (P ≤ 0.05) increased in CT/GR group. Serum concentrations of immunoglobulin M (IgM) (P ≤ 0.05) and tumor necrosis factor-alpha (TNF-α) were increased in the TEM/CR group; the concentration of transforming growth factor beta (TGF-β) significant (P ≤ 0.05) increased in the TEM/GR group; and interleukins (IL6 and IL10) showed no significant differences among the groups. Our results showed increase in thyroxine and myostatin concentrations with TES/CR and CT/GR of our study groups, respectively. The relative mRNA expression levels of the GH, IGF-1, and Fas cell surface death receptor (FAS) genes were significantly (P ≤ 0.05 and 0.01) upregulated in the liver tissue of the TEM/GR group compared with the other groups. In conclusion, TEM/GR was the best treatment for improving prehatch quality, increasing serum antioxidant enzyme activities, and promoting the expression of growth and immune genes in fertilized quail eggs.

DNA methylation of GDF-9 and GHR genes as epigenetic regulator of milk production in Egyptian Zaraibi goat

BackgroundDNA methylation is an epigenetic mechanism that takes place at gene promoters and a potent epigenetic marker to regulate gene expression.ObjectiveThe study aimed to improve the milk production of Zaraibi goats by addressing the methylation pattern of two milk production-related genes: the growth hormone receptor (GHR) and the growth differentiation factor-9 (GDF-9).Methods54 and 46 samples of low and high milk yield groups, respectively, were collected. Detection of methylation was assessed in two CpG islands in the GDF-9 promoter via methylation-specific primer assay (MSP) and in one CpG island across the GHR promoter using combined bisulfite restriction analysis (COBRA).ResultsA positive correlation between the methylation pattern of GDF-9 and GHR and their expression levels was reported. Breeding season was significantly effective on both peak milk yield (PMY) and total milk yield (TMY), where March reported a higher significant difference in PMY than November. Whereas single birth was highly significant on TMY than multiple births. The 3rd and 4th parities reported the highest significant difference in PMY, while the 4th parity was the most effective one on TMY.ConclusionThese results may help improve the farm animals' milk productive efficiency and develop prospective epigenetic markers to improve milk yield by epigenetic marker-assisted selection (eMAS) in goat breeding programs.

Growth Axis Somatostatin, Growth Hormone Receptor, and Insulin-like Growth Factor-1 Genes Express and Are Affected by the Injection of Exogenous Growth Hormone in Chinemys reevesii.

In this study, to explore the effect of growth hormone changes on the related genes and regulatory roles of the turtle, PCR amplification, real-time fluorescence quantitative analysis, and enzyme cutting technology were used to clone and sequence the somatostatin (SS) gene, growth hormone receptor (GHR), and insulin-like growth factor-1 (IGF-I) sequence of Chinemys reevesii. The effects of human growth hormone on the mRNA expression of growth-axis-related genes SS, GHR, and IGF-1 in different sexes were observed. The study of the SS gene in turtles using real-time fluorescence quantitative PCR showed that the SS gene was mainly expressed in the nervous system and the digestive system, with the highest expression found in the brain, while the GHR gene and the IGF-I gene were expressed in all tissues of Chinemys reevesii. The SS gene was expressed in the brain, pituitary, liver, stomach, and intestine, with the highest expression in the brain and the lowest expression in the liver. Within 4 weeks of the injection of exogenous growth hormone, the expression level of the SS gene in the brain of both sexes first increased and then decreased, showing a parabolic trend, and the expression level of the experimental group was lower than that of the control group. After the injection of growth hormone (GH), the expression of the GHR gene in the liver of both sexes showed a significant increase in the first week, decreasing to the control group level in the second week, and then gradually increasing. Finally, a significant level of difference in the expression of the GHR gene was reached at 3 and 4 weeks. In terms of the IGF-I gene, the changing trend of the expression level in the liver was the same as that of the GHR gene. After the injection of exogenous growth hormone, although the expression of the SS gene increased the inhibition of the secretion of the GHR gene by the Reeves' turtle, exogenous growth hormone could replace the synthesis of GH and GHR, accelerating the growth of the turtle. The experiments showed that the injection of recombinant human growth hormone affects the expression of SS, GHR, and IGF-1 genes, and promotes the growth of the Reeves' turtle.

Effects of feeding diets with zinc-l-selenomethionine on growth performance of broilers subjected to cyclic heat stress.

Limited information exists on the use of zinc-l-selenomethionine (Zn-L-SeMet) in broiler diets and its effects on the growth performance, body temperature, mortality rates, blood profile, and gene expression, especially when animals are reared under cyclic heat stress conditions. This study aimed to investigate the impact of Zn-L-SeMet in broiler diets from 1 to 42days of age reared under cyclic heat stress and its effects on growth performance, cloacal temperatures, mortality rate, blood parameters, and insulin-like growth factor 1 (IGF-1) and growth hormone receptor (GHR) gene expression in the breast muscle. A total of 1000 male Cobb 500® broiler chicks were randomly assigned to five treatments: 0, 0.15, 0.23, 0.47, and 1.30mg/kg of Zn-L-SeMet. Each treatment consisted of 10 replicates with 20 birds each. No statistically significant differences in growth performance were observed from 1 to 21days of age (P > 0.05). However, from 1 to 42days, feed intake (FI) and feed conversion ratio (FCR) decreased linearly (P < 0.05). Cloacal temperatures showed no significant effects (P > 0.05), while overall mortality rate exhibited a quadratic response (P < 0.05), with the optimal inclusion level predicted to reduce broiler mortality at 0.71mg/kg. Triglyceride (TRG) levels increased with 0.97mg/kg (P < 0.05), and gama-glutamil transferase (GGT) levels decreased with the inclusion of 1.19mg/kg (P < 0.05). No significant effects on IGF-1 and GHR gene expression were found (P > 0.05). In conclusion, the inclusion of 1.30mg/kg of Zn-L-SeMet in diets of heat-stressed broilers improved growth performance from 1 to 42days of age. An inclusion of 0.71mg/kg reduced mortality rate, while 0.97mg and 1.19mg increased and reduced TRG and GGT levels, respectively.

THU051 GH Resistance And Adipose Tissue: Multispecies Measurement Of Morphology And Transcriptome

Abstract Disclosure: J.A. Young: None. A. Hinrichs: None. S.R. Bell: None. M. Soneson: None. D.K. Geitgey: None. E. Wolf: None. E.O. List: None. J.J. Kopchick: None. D.E. Berryman: None. Laron Syndrome (LS) is a condition caused by mutations in the growth hormone (GH) receptor gene that renders the individual GH resistant. LS was first described in humans in the 1960’s, and since then, animal models of LS have been developed, including pigs (GHR-KO pigs). One of the notable characteristics of LS, in both humans and animals, is obesity without some of its comorbidities, such as increased cancer and diabetes. The aim of this study was to examine the subcutaneous and visceral adipose tissue of GH resistant pigs and a human with LS using histology and transcriptomics and make cross-species and cross-depot comparisons where possible. Adipocyte sizing analysis showed that GH resistance resulted in a trend towards increased cell sizes in human subcutaneous (SubQ) and visceral (Visc) depots, and a significant increase in pig Visc. Interestingly, the human adipocyte size histogram was similar to that of the pig across genotypes and depots. When examining the adipose transcriptome, PCA analysis showed a strong species clustering, but not a strong depot or genotype clustering. Differentially expressed gene (DEG) analysis comparing GHRKO pigs to their respective wild type controls showed that IGF1 expression was decreased in both depots, as expected, and 38 other genes were also significantly altered in GHR-KO pigs compared to controls, in both depots. Enrichment analysis showed a decrease in an extracellular matrix term in the GHR-KO SubQ compared to controls, while terms associated with fatty acid and carbohydrate metabolism were increased in GHR-KO SubQ. When comparing GHR-KO visceral to WT, terms associated with IGF signaling and longevity regulation had decreased expression, while immune activation and cell motility were increased. Pathway analysis generally agreed with these results, but also showed a decrease in multiple signaling pathways including AMPK and PI3K-Akt in both depots. Paradoxically, the JAK-STAT signaling pathway was increased in GHR-KO Visc compared to controls. Depot differences were also explored using this dataset. Within each genotype, the gene expression of the SubQ and Visc depots resulted in no significant DEGs between depots in the WT pigs, while GHRKO pigs had 24 DEGs between SubQ and Visc. Enrichment analysis and pathway analysis showed no significant results in either depot, presumably due to the low number of DEGs. In conclusion, GHR-KO pigs had expected changes in adipocyte size and expression of metabolic and extracellular matrix genes, but other unexpected changes were also present, including changes to cell motility-related genes. There were few differences between depots within each genotype, indicating that depots are equally affected by GH. Further studies are required to understand the functional changes to adipose tissue caused by LS and the effectiveness of pigs as an LS model. Presentation: Thursday, June 15, 2023

THU157 Epigenetic Regulation Of Genes Involved In The Signaling Cascade Of The GH Axis - IGF1 And Insulin. Implication In Children Postnatal Growth

Abstract Disclosure: L. Zoff: None. F. Garcia: None. G. Aschettino: None. G. Veneruzzo: None. M.C. Mattone: None. N. Perez Garrido: None. M. Juanes: None. N.I. Saraco: None. C. Alonso: None. G. Guercio: None. A. Belgorosky: None. M.S. Baquedano: None. Growth is influenced by genetic, nutritional, environmental, and hormonal factors, but it proceeds in a predictable pattern characterized by a constant growth deceleration between childhood and adolescence. This growth deceleration is coordinated in tissues and organs in order to maintain body proportions. Growth hormone (GH)/ insulin-like growth factor type 1 (IGF1) axis and insulin are crucial stimulators of growth, cell proliferation and metabolism. However, their levels do not change with age in a pattern that would explain the prepubertal decline in growth rate. DNA methylation represents a fundamental epigenetic mark that is associated with transcriptional repression during development. We hypothesize that the postnatal growth pattern could be orchestrated by epigenetic mechanisms. In order to analyze age related physiological changes, we evaluated promoter methylation in the GHR, IGF1R and INSR genes in peripheral blood from 40 healthy children of both sexes (females (F) n=21 and males (M) n=19), between 3 and 15 years old by using targeted deep-amplicon bisulfite sequencing on a MiSeq system. Sequencing libraries of 4 promoter CpG rich regions for GHR, 3 for IGF1R and 5 for INSR (104, 103 and 141 CpG sites, respectively) were analyzed for mean methylation values of all CpG sites using amplikyzer2 software. The results would suggest a sexual dimorphism in the epigenetic regulation of GH, IGF1 and insulin receptors gene expression. A significant negative correlation between GHR methylation and age was observed in both sexes (Multiple Spearman correlation, p&amp;lt;0.05), but in different GHR promoter regions. Specifically, a decrease in themethylation levels with age were detected in CpG-8, CpG+183 and CpG+243 in F; and in CpG+343, CpG+346, CpG+385, CpG+391, CpG+407 and CpG+487 in M. In contrast, in the IGF1R promoter region, a positive correlation was observed exclusively in F, between mean methylation levels and age in CpG-51, CpG-43, CpG-41, CpG-23, CpG-17, CpG-15, CpG-13, CpG-11, and CpG-9, p&amp;lt;0.05. Male-specific positive correlation between INSR promotermethylation values and age were found in CpG-768, CpG+10, CpG+31, CpG+87, CpG+95, CpG+163, CpG+199, CpG+206, CpG+238, CpG+700, CpG+815 and CpG+900, p&amp;lt;0.05.Taking together, our findings are in agreement with the hypothesis that age-associated DNA promoter methylation changes could be involved in the physiological growth pattern. Finally, the observed sexual dimorphism suggests age- and sex-dependent regulatory mechanisms for normal growth. Presentation: Thursday, June 15, 2023