GH Gene Research Articles

Autosomal Dominant Growth Hormone Deficiency Due to a Novel c.178G>A Mutation in the GH1 Gene is Caused by Alternative Splicing to Produce a Small GH Isoform

IntroductionGrowth hormone (GH) is a member of the somatotropin/prolactin family of hormones and plays a vital role in human physiology. Mutations in GH1 cause isolated growth hormone deficiency. Several disease‐causing mutations have been reported in patients with IGHD. The most frequent cause of familial growth hormone deficiency (GHD) is Type II autosomal dominant GHD (isolated GHD type II) due to several heterozygous GH1 mutations. These mutations have been shown to (a) produce shorter isoforms of GH that do not bind to growth hormone receptors, (b) cause diminished secretion of GH, or (c) result in misfolded GH protein.MethodsGenomic DNA from patients with familial GHD was enriched for the coding exons using hybrid capture technology, and GH1 was sequenced. The p.A34T mutant protein was expressed in bacteria, and binding to GHR was studied by Surface Plasmon Resonance technology. Computational prediction of transcription indicated that alternative splicing is likely to produce a shorter GH variant with skipping of exon 3 in GH1. Mammalian cell‐based studies incorporating transfections of the whole GH1 gene containing all exons and introns, were used to study transcriptional effects. RNA was isolated from cells transfected with WT and mutant GH1 gene and analyzed by RT PCR using primers in the second and fifth exons of GH1 that could identify all possible isoforms of GH1 mRNA.ResultsGHD was identified in three female siblings aged 3.25–6.33 years (Ht SDS −3.21 to −1.13, peak GH 2.9–6.6 ng/mL); their mother had previously been diagnosed with GHD at age 12.33 years (Ht SDS −3.44, GH peak < 2 ng/mL). Sequencing of GH1 identified a novel heterozygous variant (c.178G>A; p.Ala34Thr) not found in the Broad ExAc dataset representing >60,000 children without the severe childhood‐onset disease. Functional studies using whole gene transfection showed that the c.178G>A mutation leads to alternate splicing resulting in increased production of the shorter 17.5kD isoform of GH due to exon 3 skipping. Results were confirmed by quantitative RT‐PCR as well as GH secretion assays, which showed a lower level of GH production from cells transfected with the GH1 gene containing the c.178G>A mutation. The SPR based receptor binding assay and cell proliferation assay using bacterially expressed proteins showed that once produced, the GH protein with the A34T mutation behaves similar to WT GH protein. All these results confirm that the cause of GHD due to the c.178G>A mutation in GH1 is due to altered transcription leading to the production of the shorter 17.5 kD isoform of GH protein and not due to the amino acid change A34T that is caused by the mutation.ConclusionThe presence of a heterozygous GH1 variant (c.178G>A, p.Ala34Thr) in four individuals with GHD suggests that this is a novel cause of IGHD type II. Production of the smaller 17.5 kD GH isoform results in reduced overall GH secretion and loss of binding to GHR due to competition with the normal GH protein, explaining the dominant‐negative phenotype.Support or Funding InformationUnrestricted research grants from Novo Nordisk AG, & Sandoz Pharmaceuticals AG, Switzerland.

Short stature explained by dimerization of human growth hormone induced by a p.C53S point mutation

A homozygous mutation in growth hormone 1 (GH1) was recently identified in an individual with growth failure. This mutation, c.705G>C, causes replacement of cysteine at position 53 of the 191-amino-acid sequence of 22 kDa human GH (hGH) with serine (p.C53S). This hGH molecule (hereafter referred to as GH-C53S) lacks the disulfide bond between p.Cys-53 and p.Cys-165, which is highly conserved among species. It has been reported previously that monomeric GH-C53S has reduced bioactivity compared with WT GH (GH-WT) because of its decreased ability to bind and activate the GH receptor in vitro In this study, we discovered that substitution of p.Cys-53 in hGH significantly increased formation of hGH dimers in pituitary cells. We expressed His-tagged hGH variants in the cytoplasm of genetically modified Rosetta-gami B DE3 Escherichia coli cells, facilitating high-yield production. We observed that the bioactivity of monomeric GH-C53S is 25.2% of that of GH-WT and that dimeric GH-C53S-His has no significant bioactivity in cell proliferation assays. We also found that the expression of GH-C53S in pituitary cells deviates from that of GH-WT. GH-C53S was exclusively stained in the Golgi apparatus, and no secretory granules formed for this variant, impairing its stimulated release. In summary, the unpaired Cys-165 in GH-C53S forms a disulfide bond linking two hGH molecules in pituitary cells. We conclude that the GH-C53S dimer is inactive and responsible for the growth failure in the affected individual.

Polymorphism of <i>CAST, GH, GDF9</i> genes of Gorno-Altai sheep breed

The results of studying the genetic diversity of local breeds of farm animals are presented. The object of research is the Gorno-Altai mutton-wool breed of sheep, maximally adapted to the harsh climatic conditions of the Altai mountains, and year-round pasture use. The breed is rich in milk, which ensures high survival rate of young animals. The genes and their polymorphic variants associated with breeding traits of sheep were studied. The genes of Calpastatin ( CAST ), Somatotropin ( GH ), and differential growth factor ( GDF9 ) are considered as promising genes marking qualitative and quantitative traits of meat productivity in sheep. The analysis of the DNA diagnostics results revealed that the polymorphism of the CAST , GH , GDF9 genes is represented by two alleles, M and N; A and B; A and G, respectively, and three genotypes – MM, NN, MN; AA, BB, AB; AA, GG, AG with different frequency of occurrence. The frequency of the desired N allele of the CAST gene was 27.5%, the B allele of the GH gene 37.5%, and the A allele of the GDF9 gene 45.0%. A comparative analysis of the level of actual and theoretical expected heterozygosity indicates the ambiguity of the nature of their distribution depending on the gene. The highest indicators of actual and expected heterozygosity were characteristic of the GDF9 gene, which amounted to 0.538 and 0.651, respectively, against 0.290 and 0.368; 0.290 and 0.445 for the CAST and GH genes. The highest (36.9%) degree of genetic variation (V) was characteristic of the GDF9 gene at 24.4%, and 28.3% for the CAST and GH genes. The variability of the heterozygosity test changeability in the studied genes was noted to be not significant: from minus 0.08 for the CAST gene to minus 0.15 and minus 0.11 for the GH and GDF9 genes, which indicates a certain lack of heterozygotes. The research results showed the prospect of including testing, selection and assortment of the studied genes into breeding programs for improving the Gorno-Altai breed of sheep.

The Transcription Factor NR4A2 Plays an Essential Role in Driving Prolactin Expression in Female Pituitary Lactotropes.

Differentiation of the hormone-producing cells of the pituitary represents an informative model of cell fate determination. The generation and maintenance of 2 pituitary lineages, the growth hormone (GH)- producing somatotropes and the prolactin (PRL)- producing lactotropes, are dependent on the pituitary-specific transcription factor, POU1F1. While POU1F1 is expressed in both cell types, and plays a role in activation of both the Gh and Prl genes, expression of Gh and Prl is restricted to somatotropes and lactotropes, respectively. These observations imply the existence of additional factors that contribute to the somatotrope and lactotrope identities and their hormone expressions. Prior transcriptome analysis of primary somatotropes and lactotropes isolated from the mouse pituitary identified enrichment of a transcription factor, Nr4a2, in the lactotropes. Nr4a2 was shown in a cell culture model to bind the Prl promoter at a position adjacent to Pou1f1 and to synergize with Pou1f1 in driving Prl transcription. Here we demonstrate in vivo the role of Nr4a2 as an enhancer of Prl expression by conditional gene inactivation of the Nr4a2 gene in mouse lactotropes. We demonstrate that nuclear orphan receptor transcription factor (NR4A2) binding at the Prl promoter is dependent on actions of POU1F1; while POU1F1 is essential to loading polymerase (Pol) II on the Prl promoter, Nr4a2 plays a role in enhancing Pol II release into the Prl gene body. These studies establish an in vivo role of Nr4a2 in enhancing Prl expression in mouse lactotropes, explore its mechanism of action, and establish a system for further study of the lactotrope lineage in the pituitary.

A cross-sectional study exploring disease characteristics and phylogenetic nature of human cytomegalovirus among infected neonates with congenital nephrotic syndrome.

Congenital nephrotic syndrome (CNS) is a rare but serious condition which affects neonates and is caused by monogenic defects of glomerular structural proteins or congenital viral infections. Several reports have established a causal relationship between human cytomegalovirus (HCMV) intrauterine infection and CNS, but thorough study assessing parameters has not yet been done. This study aimed to ascertain significant demographic, biochemical, serological, inflammatory and etiological parameters with 12months follow-up to clinically identify and monitor neonates with HCMV-associated CNS and sought to decipher the phylogenetic nature of infecting strains. Differences between four patient groups (neonates < 4weeks old) with or without CNS and HCMV infection were compared by unpaired t testing and one-way analysis of variance (ANOVA). Linear regression was performed to assess statistical significance among individual groups. Maximum-likelihood-based phylogenetic analysis was performed with HCMV gH gene sequences to compare clinically isolated and referenced NCBI strains. This was further supported by analysis of effective number of codons (ENc), codon adaptation index (CAI) and mRNA structural variation. Patients with HCMV-associated CNS were found to have significant variations in many studied parameters compared with controls. The majority of clinical strains formed a separate phylogenetic cluster defining them as somewhat distinct from standard reference strains, which was supported by the other analyses. This study defined parameters for monitoring cases of HCMV-associated CNS, which suggest the possible existence of a selection force acting and rendering these HCMV strains able to infect selective host tissues and cause specific disease types.

Growth Hormone Gene Polymorphisms in Mature Healthy Male Muscovy Ducks in Egypt

Blood samples were obtained from 28 mature healthy male Muscovy ducks for screening of a partial sequence of Growth hormone gene (GH gene) for single nucleotide polymorphisms using PCR amplification of the extracted DNA. The results of our research revealed one locus of exon 2 of growth hormone gene and its partial flanking intron. Polymorphisms in this locus were investigated by using direct sequencing and single strand conformational polymorphism (SSCP) technique. One unique pattern of SSCP was detected. Nucleotide sequencing was performed to endorse the current result which proved the absence of single nucleotides' polymorphisms (SNPs) or any other type of polymorphisms in the studied locus. The DNA sequencing and PCR-SSCP patterns confirmed that there was no polymorphism in all studied birds. In turn, it is spelled that PCR-SSCP failed to produce electrophoresis patterns capable of discriminating between the GH gene loci in Muscovy duck breed revealing no polymorphism in all studied individuals. Also, we compared our sequences with the published sequence on the gene bank of GH gene in Mallard ducks under the following accession number AB158762.1. Three SNPs were detected between Muscovy and Mallard breeds which are (94 A-G, 271 C-T and 298 G-A) these SNPs led to change of two amino acids proline and valine amino acids in GH protein in mallard ducks into serine and isoleucine in Muscovy ducks. In conclusion, these changes in the nucleotide sequence, amino acid and protein chain may be the main cause of differences of the phenotypic features, productive and reproductive traits between Muscovy and mallard duck breeds.

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.

MiR-709 inhibits GHRP6 induced GH synthesis by targeting PRKCA in pituitary

Pituitary growth hormone (GH) plays an essential role in processes of organism growth and metabolism. MicroRNA (miRNA) could also participate in diverse biological processes. However, the role of miRNA in the regulation of pituitary GH during the growth process remains unclear. In this study, we firstly confirmed that the second highly expressed pituitary miRNA (miR-709) significantly inhibited the GH synthesis and suppressed the viability of GH3 cells. The bioinformatics analysis and dual luciferase report system were used to ascertain the PRKCA is the direct target gene of miR-709, which is the coding gene of PKCα. Then the transcription and translation levels of Prkca were obvious reduced by the over-expression of miR-709 in GH3 cells, followed by the inhibition of the transcription factor (CREB1) of Gh1 gene and the ERK1/2 signaling pathway or the possible cross-talk signaling pathway (cAMP/PKA signaling pathway) detected by western blot, suggesting that ERK1/2 maybe an important factor involved in the GH3 cell viability mediated by PKCα. At last, GHRP6 increased PKCα and GH expression but reduced miR-709 expression in vitro and vivo assays, and this conclusion was further confirmed by the result of GHRP6 attenuated the inhibition of miR-709 on GH expression. These findings will provide new molecular mechanism on the regulation of pituitary GH.

A mutation map for human glycoside hydrolase genes.

Glycoside hydrolases (GHs) are found in all domains of life, and at least 87 distinct genes encoding proteins related to GHs are found in the human genome. GHs serve diverse functions from digestion of dietary polysaccharides to breakdown of intracellular oligosaccharides, glycoproteins, proteoglycans and glycolipids. Congenital disorders of GHs (CDGHs) represent more than 30 rare diseases caused by mutations in one of the GH genes. We previously used whole-exome sequencing of a homogenous Danish population of almost 2000 individuals to probe the incidence of deleterious mutations in the human glycosyltransferases (GTs) and developed a mutation map of human GT genes (GlyMAP-I). While deleterious disease-causing mutations in the GT genes were very rare, and in many cases lethal, we predicted deleterious mutations in GH genes to be less rare and less severe given the higher incidence of CDGHs reported worldwide. To probe the incidence of GH mutations, we constructed a mutation map of human GH-related genes (GlyMAP-II) using the Danish WES data, and correlating this with reported disease-causing mutations confirmed the higher prevalence of disease-causing mutations in several GH genes compared to GT genes. We identified 76 novel nonsynonymous single-nucleotide variations (nsSNVs) in 32 GH genes that have not been associated with a CDGH phenotype, and we experimentally validated two novel potentially damaging nsSNVs in the congenital sucrase-isomaltase deficiency gene, SI. Our study provides a global view of human GH genes and disease-causing mutations and serves as a discovery tool for novel damaging nsSNVs in CDGHs.

The acute effects of growth hormone in adipose tissue is associated with suppression of antilipolytic signals.

AimSince GH stimulates lipolysis in vivo after a 2‐hr lag phase, we studied whether this involves GH signaling and gene expression in adipose tissue (AT).MethodsHuman subjects (n = 9) each underwent intravenous exposure to GH versus saline with measurement of serum FFA, and GH signaling, gene array, and protein in AT biopsies after 30–120 min. Human data were corroborated in adipose‐specific GH receptor knockout (FaGHRKO) mice versus wild‐type mice. Expression of candidate genes identified in the array were investigated in 3T3‐L1 adipocytes.ResultsGH increased serum FFA and AT phosphorylation of STAT5b in human subjects. This was replicated in wild‐type mice, but not in FaGHRKO mice. The array identified 53 GH‐regulated genes, and Ingenuity Pathway analysis showed downregulation of PDE3b, an insulin‐dependent antilipolytic signal, upregulation of PTEN that inhibits insulin‐dependent antilipolysis, and downregulation of G0S2 and RASD1, both encoding antilipolytic proteins. This was confirmed in 3T3‐L1 adipocytes, except for PDE3B, including reciprocal effects of GH and insulin on mRNA expression of PTEN, RASD1, and G0S2. Conclusion (a) GH directly stimulates AT lipolysis in a GHR‐dependent manner, (b) this involves suppression of antilipolytic signals at the level of gene expression, (c) the underlying GH signaling pathways remain to be defined.

Laboratory investigations in the diagnosis and follow-up of GH-related disorders.

In addition to auxiological, clinical and metabolic features measurements of growth hormone (GH) and insulin-like growth factor I (IGF-I) complement our tools in diagnosis and follow-up of GH-related disorders. While comparably robust during the pre-analytical phase, measurement and interpretation of concentrations of both hormones can be challenging due to analytical issues and biological confounders. Assay methods differ in terms of antibody specificity, interference from binding proteins, reference preparations and sensitivity. GH assays have different specificity towards different GH-isoforms (e.g. 20 kDa GH, placental GH) and interference from the GH antagonist Pegvisomant. The efficacy to prevent binding protein interference is most important in IGF-I assays. Methodological differences between assays require that reference intervals and diagnostic cut-offs are assay-specific. Among biological variables, pubertal development and age are most relevant for IGF-I, making detailed reference intervals mandatory for interpretation. GH has pulsatile secretion and short half-life. Its concentration is modified by acute factors such as stress, exercise and sleep, but also by intake of oral estrogens and anthropometric factors (e.g. BMI). Other GH dependent biomarkers such as free IGF-I, IGF binding protein 3 (IGFBP 3) and acid labile subunit (ALS) have been proposed. Their concentrations largely mirror the information obtained through measurement of IGF-I, but their measurement can be helpful in particular situations. In this review, we describe the evolution of analytical methods to measure biomarkers of GH action, the impact of the methodological changes on laboratory results and the need to include biological variables in their interpretation. Arch Endocrinol Metab. 2019;63(6):618-29.

Features of polymorphism of calpastatin and somatotropin genes in young sheep, obtained from crossing ewes of Kalmyk fat-rumped sheeps and dorper rams

The article presents the study of polymorphism of the CAST and GH genes, which determine the features of the manifestation of the productive and biological characteristics of sheep with ½ Kalmyk + ½ Dorper blood system. Calpastatin gene polymorphism represented by alleles M and N, whose frequency was 0,65 and 0,35; genotypes MM, MN – 30 and 70% accordingly. The desired NN genotype has not been identified. A relatively uniform incidence of allele N (0,35) CAST gene and B (0,40) GH was established, what contributed to an almost equal distribution of allele frequencies М (0,65) and А (0,60) genes of calpastatin and somatotropin accordingly. The frequency of heterozygous genotypes occurrence by CAST gene composed 0,7. By GH gene the following distribution of genotype frequencies is observed. Frequency of occurrence homozygous АА and heterozygous AB genotypes was equal to and is 0,4, wherein the frequency of occurrence advised homozygous ВВ genotype was 0,2. Among the animals studied, sheep with a complex genotype are most common CASTMNGHAB (40 %). The amount of percent CASTMMGHAA and CASTMNGHAA is in 22,2%. 10% is for genotypes CASTMMGHBB and CASTMNGHBB.

Diet Effects on Growth, Mortality, RNA: DNA Ratio and Gene Expression of Zebrafish Danio rerio

This study evaluated the effects of different combination of commercial and natural diets (T1: egg yolk, T2: egg yolk+ Artemia, T3: Horlicks, T4: Horlicks+ Artemia, T5: TetraBits, T6: TetraBits+ Artemia, T7: NovoTom, T8: NovoTom+ Artemia) on growth, mortality, RNA: DNA ratio and gene expression of zebrafish for a period of 45 days. Significantly highest length (2.75±0.04 cm) and weight (0.25±0.10 g) gain were recorded in T2 treatment. Lowest length gain (2.00±0.08 cm) and weight gain (0.14±0.12 g) were calculated in T3. Significant highest mortality (65.00±8.66%) was observed in treatment T7 followed by T5 and T8 and significant lowest mortality (20.00±7.64%) was recorded in T2. By molecular analysis, Highest RNA: DNA ratio was found (1.01) in T5 followed by T4 (0.95) and lowest was found in T1 (0.77). Interestingly, a similar result was observed for gh1 (Growth hormone 1) gene expression. Highest gene expression was found in T5 followed by T4 and lowest in T2. Significant down regulation was observed in T2 for gh1 gene. Finally, the study would suggest that zebrafish can be fed with egg yolk+Artemia for better growth performance. The findings could provide a significant contribution to the field of global zebrafish as well as aquaculture research.

Особливості екстерʼєру голштинських корів різних генотипів

This study presents the results of the relationship of various polymorphic variants of the GH and PIT-1 gene with the exterior in highly productive Holstein cows. Experimental animals were divided into groups depending on the combination of different allele forms of GH and PIT-1 genes. PCR method was used to determine the polymorphism of marker genes. Isolation of genomic DNA was performed using resin «Chelex-100». The reaction was carried out in a thermal cycler «Tertsyk» made by «DNA technology». The research was carried out in the Private Joint Stock Company «Agro-Soiuz» Dnipropetrovsk region. The total set sample was 48 half-sibling cows, which were the daughters of the Holstein bull Kashemir 131671771. All animals were even-aged analogues. DNA samples isolated from the peripheral blood of the experimental animals were examined. Restrictase AluI was used for the GH gene restriction. After restriction, 171 bp and 52 bp long fragments were detected in representatives of the LL genotype, and a non-restriction fragment with a length of 223 bp was found in carriers of the VV genotype. Restriction of the amplified fragment of RIT-1 gene was performed using restriction endonuclease HinfI. Fragments 660 bp, 425 bp, and 270 bp long, after processing the PCR products with HinfI restriction endonuclease, corresponded to the A allele; fragments 660 bp, 385 bp, and 270 bp long indicated the B allele. Restriction products were separated by electrophoretic method in 2% agarose gel in Tris Borate EDTA. Measurements and exterior indices studies were performed during the 2nd-3d months of the second lactation. It was found that cows of the LL / AB genotype complex compared with their peers of LV/BB and LL/BB genotypes were higher at the withers and sacrum by 3.1 and 2.9 cm, respectively (2.1 and 1.9%; at P &gt; 0, 99). It was determined that the skin in the middle of the last rib of the LL / AB genotype cows compared to peers of LV/BB genotype was thinner by 0.5 mm (9.6%) at P &gt; 0.95. Other measurements of the exterior in the investigated groups of animals differed little. Peers of LL/BB genotype took an intermediate position in these traits. The strength of the complex genotype influence on the features of the exterior was in the range from 2.7 to 12.6%. Holstein cows of the LL/AB genotype had a significant difference in the mass index by 3.3% at P &gt; 0.95, as well as a slightly larger body volume by 28 134.9 cm3 (3.4%), a lower body density index by 0.037 g/cm3 (4.7%) compared with peers of the LV/BB genotype. It is proposed to select animals with the following LL/AB and LL/BB alleles in the complex genotype in order to obtain cows with a better exterior features.

Association of CAPN1 and GH genes with productivity traits in Kazakh Whiteheaded cattle

The Kazakh Whiteheaded cattle was developed by crossing local breeds with the Hereford breed in Kazakhstan in the 30s of the last century. This breed is adapted to arid conditions of extreme continental climate. The goal of the investi-gations was the assessment of the genetic structure of the Kazakh Whiteheaded breed based on the genes of calpain (CAPN1) and somatotropic hormone (GH) and analysis of the association of genotypes for these genes with productivity traits. The main argument for this aim is research works illustrated that both genes could affect on meat productivity traits in other breeds of cattle. 352 blood samples from representatives of Kazakh Whiteheaded animals of different sex and age groups were genotyped for the CAPN1 and GH loci. As a result, it was firstly proved that Kazakh Whiteheaded animals, who are CC homozygosis at the CAPN1 locus and VV homozygosis at the GH locus, reliably exceed animals without C and V alleles on the productivity traits such as milk production, average daily body weight gain, and pre-slaughter body weight, slaughter weight, carcass weight, flesh weight, chemical composition and histological characteristics of meat. It was also shown that the frequencies of the desired alleles and genotypes of these loci are rather low the frequency of the C allele was 0.11–0.17, and the frequency of the CC genotype was 0.03–0.06 in different age and sex groups; the frequency of the V allele was 0.19-0.40, and the frequency of the VV genotype was 0.03-0.31. Thus, planning selection for Kazakh Whiteheaded cattle, it would be useful to take into account the assessment of ani-mal genotypes at the CAPN1 and GH loci to increase the proportion of animals with the desired genotypes.

The Relationship between Pesticide Exposure and Umbilical Serum IGF-1 Levels and Low-birth Weight: A Case-control Study in Brebes, Indonesia.

Background: Birth weight is very important for long-term physical, mental, health, and brain development. Pesticide exposure is thought to interfere with fetal growth, among others, through disruption of the function of the insulin-like growth hormone-1 (IGF-1) hormone. Objective: To analyze the relationship between exposure to pesticides during pregnancy and low-birth weight (LBW) through the disruption of the IGF-1 hormone. Methods: In a case-control study, babies born with LBW (birth weight <2500 g) and those born later with normal birth weight (≥2500 g) at 2 hospitals in Brebes were chosen as cases and controls, respectively. Maternal pesticide exposure was measured by interview using a questionnaire. Umbilical serum IGF-I level was tested using the ELISA method. Results: There was a significant relationship between pesticide exposure during pregnancy and LBW (OR 6.8; 95% CI 2.0 to 22.9) and low umbilical serum IGF-1 levels (OR 3.6; 95% CI 1.2 to 11.1). There was a significant relationship between low umbilical serum IGF-1 levels and LBW (OR 8.9; 95% CI 2.4 to 32.1). Conclusion: There was a significant relationship between pesticide exposure during pregnancy and LBW through the umbilical serum IGF-1 reduction pathway.

Exon and Intron Variability in Salmonidae Growth Hormone Genes

Gene duplication is one of the main mechanisms of formation of new genetic material in evolution. The occurrence of a gene duplication is believed to relax selection pressure on one of the copies. Consequently, this gene accumulates mutations at a higher rate, and over time it acquires a new function. As a result of several rounds of polyploidization, many genes in salmon are duplicated, including the growth hormone gene. The analysis of nucleotide diversity in the paralogous genes of growth hormone, gh1 and gh2, demonstrated that the level of variability in their introns was higher than in the exons. In addition, the variability of each exon weakly correlated with its length, and seems to be determined by the functional significance of the protein region encoded. The level of variability in the exons of the gh2 gene was higher than that in the gh1 one, which was probably due to the current process of gene subfunctionalization.

Dynamics of gene expression of hormones involved in the growth of broiler chickens in response to the dietary protein and energy changes

The synergy between the genetic potential and the nutrient intake determines the growth performance of meat-type chicken and nutrigenomics approach helps us understand the response of candidate genes of growth in chicken to dietary manipulations. The current study aimed to assess the growth performance and expression of hepatic growth related genes in the naked neck broiler chicken in response to different dietary energy and protein levels with a hypothesis that high plane of nutrition enhances both of these positively. The results revealed that birds have shown significantly better growth performance under high protein (HP) and high energy (HE) dietary regime. The expression profiles of the genes studied revealed upregulation of IGF-1, IGF-2, and GH under dietary HP and HE regime relative to other protein and energy levels with greater upregulation at 3rd week than the 1st and 5th week of age of birds. The IGFR and GHR mRNA expression was significantly higher under HP and HE dietary regimen with an increasing and decreasing trend from 1st to 5th week of age, respectively. A consistent and significant downregulation of IGFBP-2 was observed under HP and HE regime throughout the feeding trial. The myostatin expression was higher at 3rd week of age followed by 1st week expression. The HP and HE as well as LP (Low protein) and HE diet resulted in significant upregulation of myostatin gene expression in liver. In support to the set hypothesis of this study the high protein and high energy diet resulted in better growth performance of broiler chickens with corresponding upregulation of IGF-1, IGF-2, IGFR, GH, GHR, and Myostatin gene expression and downregulation of IGFBP-2 in liver.

Growth hormone 1 and insulin 2 gene polymorphism in Egyptian chickens

The genetic polymorphism of two genes related to growth production in four chicken breeds (Dokki 4, Inshas, El-Salam and Mandarah) were studied. PCR-RFLP and single nucleotide polymorphism (SNPs) analysis were studied in the two genes namely GH1 and insulin 2. Blood samples were collected randomly from 84 chickens, DNA was extracted and genotypes for two genes were detected using PCR-RFLP analysis. The locus GH1 (467 bp) showed two genotypes (GG, AG) in four chicken breeds due to the presence of two Msp1 restriction sites (C^CGG) in intron1. The sequence analysis revealed two substitutions (C/T) in Dokki 4 and Inshas breeds, G/A substitution in Dokki 4 and Mandarah breeds and insertion of T nucleotide in four chicken breeds. In insulin 2 gene (371 bp), two genotypes (TT, TC) were recorded in four chicken breeds due to presence of one restriction site in intron1. The nucleotide substitutions (A/G) and (T/C) were observed in all Egyptian chicken breeds except Inshas breed and A/ T transversion was observed in all breeds. The sequences of detected SNPs were submitted to GenBank database with the accession numbers MG906782–MG906789 in GH1 gene and the accession numbers MG906790–MG906791 in insulin 2 gene. In conclusion, the presence of certain polymorphisms could increase the phenotypic variety and will be supportive in selection and breeding programs.

Nasal Congestion and Its Management in Pregnancy Rhinitis

Background: Pregnancy rhinitis occurs approximately in one-fifth of pregnancies, at almost any gestational week. The incidence rate of pregnancy rhinitis reaches up to 40%, with prevalence as high as 17%. Pathomechanism is still unclear, but it is suspected that estrogen and placental growth hormone (PGH) play roles in the development of disease. Objective: To elaborate the pathomechanism of pregnancy rhinitis and the proper management of rhinitis symptoms, particularly nasal obstruction. Methods: Literature review. Conclusion: Pregnancy rhinitis, manifested as nasal congestion, is considered a phenomenon and may become a serious condition. Persistent nasal congestion acts as a potential risk factor in affecting fetal growth and development through gradual hypoxia process. This condition can lead to various complications such as maternal hypertension, preeclampsia, impaired fetal growth, and low APGAR scores. Indepth knowledge of pathomechanism is essential as guidance to accurate treatment including conservative and pharmaca therapies, which will lead to optimal outcome for both mother and baby.