GH Gene Research Articles

The clinical and genetic aspects of six individuals with GH1 variants and isolated growth hormone deficiency type II.

Isolated growth hormone deficiency type II (IGHD II) is an autosomal dominant disorder characterized by a GH1 gene variant resulting in a significant reduction in growth hormone (GH) secretion and a subsequent decrease of plasma insulin-like growth factor 1 (IGF-1) levels and eventual growth impairment. This study aimed to identify causative variants in six Chinese families with IGHD II, exploring both clinical and genetic characteristics. Detailed clinical data, including clinical presentations, physical charateristics, medical and family histories, as well as genetic test results, were systematically examined. Six children, comprising four males and two females, with a mean age of 4.64 ± 1.15 years, exhibited short stature with a mean height of -3.95 ± 1.41 SDS. Four of them had a family history of short stature, while one patient presented with pulmonary hypertension. All children demonstrated GH deficiency in growth hormone stimulation tests (mean peak GH value: 2.83 ± 2.46 ng/mL). Exome sequencing for the six patients and targeted gene sequencing for their family members revealed heterozygous variants in the GH1 gene, including Exon2-5del, c.334T>C, c.291 + 1G>A, c.291 + 2T>A, 1.5 kb deletion, and 1.7 kb deletion, with four variants being novel. Four patients underwent human recombinant growth hormone (rhGH) replacement therapy, initiating treatment at a mean age of 4.6 ± 0.7 years. The mean height increase in patients was 1.21 ± 0.3 SDS in the first six months of treatment and 1.79 ± 0.15 SDS in the first year. Our findings contribute to expanding the genotypic and phenotypic spectra of individuals with IGHD II.

6376 Wnt/beta-catenin Pathway is Associated with Cell Proliferation in Growth Hormone-producing Pituitary Tumors

Abstract Disclosure: S. Kuwabara: None. H. Kameda: None. H. Nomoto: None. K. Cho: None. A. Nakamura: None. Y. Ishi: None. H. Motegi: None. M. Fujimura: None. T. Atsumi: None. Objective: It has been well recognized that the Wnt/β-catenin pathway regulates cell proliferation, and that translocation of β-catenin from the cytoplasm to the nucleus promotes cell proliferation. There have been, however, limited reports on the Wnt/β-catenin pathway in growth hormone-producing pituitary tumors (GHomas), and we aimed to investigate the impact of the Wnt/β-catenin pathway on cell proliferation in GHomas. Methods: We performed three types of experiments with patient pathological specimens, disease model cell lines, and primary culture of GHoma cells. 1.The intracellular localization of β-catenin was evaluated using immunofluorescence staining of pathological specimens from GHoma patients and subsequently its association with clinical data was analyzed. 2.The Wnt/β-catenin inhibitor iCRT14 was administered to rat GHoma cells GH1, using the WST-1 assay to measure cell viability and real-time PCR to assess GH and cell cycle genes expression. 3. The Wnt/β-catenin inhibitor iCRT14 was added to cultured cells obtained from GHoma patients to evaluate cell viability and gene expression. Results: 1. Samples from 26 cases (42%) exhibited strong dot-like expression of β-catenin in the nucleus (dot pattern (DP) group), and samples from 36 cases (58%) showed β-catenin expression in the cytoplasm or cell membrane (non-DP group). Tumors in the DP group had a larger size than non-DP group (diameters 18.3±9.2 vs. 13.4±7.4 mm, p<0.05), and the postoperative remission rate was lower (23 vs. 50%, p<0.05). 2. Viability evaluation using WST-1 assay showed a maximum decrease of 25%. Gene expression showed concentration-dependent reduction in GH gene expression by up to 40% (p<0.05) and cyclin D1 gene up to 50% (p<0.05) following iCRT14 administration. 3. Among 6 cases, 3 showed a tendency toward cell growth inhibition, and 4 showed a tendency toward decreased cyclin D1 gene expression. Conclusion: It is suggested that the Wnt/β-catenin pathway is activated in the DP group because of the nucleus accumulation of β-catenin, and given the larger tumor size and lower postoperative remission rate in DP group, the Wnt/β-catenin pathway may stimulate cell proliferation in GHomas. In addition, cyclin D1-mediated effects were considered. Wnt/β-catenin pathway could play a role in GHomas growth, therefore this pathway would be a potential therapeutic target for treating affected patients. Presentation: 6/3/2024

9378 Knockdown Of The Cdh2 Gene In Zebrafish Determines Its Role In Terminal Hormone Differentiation

Abstract Disclosure: B.V. Fernandes: None. C. MacRae: None. L.R. Carvalho: None. M. Junqueira: None. Introduction: Congenital hypopituitarism (CH) is characterized by the deficiency of one or more pituitary hormones. Whole exome sequencing (WES) has allowed the identification of novel/rare variants in genetic diseases. Among CH patients, 85% lack a molecular diagnosis. WES approach in a patients born to consanguineous parents identified the homozygous variant (c.865G>A, p. Val289Ile) in the CDH2 gene that produce N-Cadherin protein responsible for cell-cell adhesion. This variant was predicted as likely pathogenic allelic variant by ACMG criteria was found in a patient with GH, TSH, ACTH, LF/FSH deficiencies associated with an ectopic neurohypophysis and pituitary hypoplasia. CDH2 analysis in a cohort of 219 patients with CH, followed in a single Brazilian center, identified 3 unrelated families with heterozygous variants and incomplete penetrance where 2 were novel, in addition to the p. Val289Ile. The deleterious effect of the homozygous variant on cell adhesion properties was confirmed in permanent transfection assays in L1 fibroblast cell lines. To determine the role of the cdh2 gene in pituitary development and hormone production and secretion, we selected zebrafish as an animal model due to its 75% genetic homology with humans. Knockout of cdh2 using Crispr/cas9 genomic edition resulted in 85% lethality of animals at 48 hours post-fertilization (hpf), precluding analysis of its role during pituitary development. Objective: To produce a cdh2 knockdown in zebrafish for phenotypic and molecular analysis. Materials and Methods: The pET28B-RfxCas13d-His plasmid was transformed, linearized, and followed by in vitro transcription to produce Cas13 mRNA. Three guide RNAs targeting the cdh2 gene were designed to guide Cas13 to the target. The Cas13/RNA guide complex was injected into single-cell embryos, and phenotypic analyses were performed under a stereomicroscope until 96 hpf. To evaluate cdh2, prop1, pit1 and gh gene expression by RT-PCR, embryos were collected at 24, 48, 72, and 96 hpf. Results: Knockdown animals exhibited microcephaly, cardiac edema, and microphthalmia during embryonic development. CDH2 expression was decreased by 75% in the first 24 hours of life and began to recover by 48 hours, gradually increasing until 96 hpf when it equaled to WT. gh expression was statistically decreased at 48h compared to WT, with an increased gh expression similar to cdh2 increasing reaching similar WT levels by 96 hpf. There was no statistically significant difference in prop1 and pit1 expression compared to WT in the analyzed periods. Conclusion: The cdh2 knockdown in zebrafish using Cas13 enzyme was effective with cdh2 decreased expression by 75% presenting a phenotype similar to the knockout model. Decreased gh expression at 48h suggests an important role of cdh2 in hormonal terminal differentiation, which should be corroborated by analysis of other hormone expressions. Presentation: 6/2/2024

ОЦЕНКА КОРОВ-ПЕРВОТЁЛОК ЧЁРНО-ПЁСТРОЙ ПОРОДЫ ПО ДНК-МАРКЕРАМ, АССОЦИИРОВАННЫХ С ХОЗЯЙСТВЕННО-ПОЛЕЗНЫМИ ПРИЗНАКАМИ

At present time are widely used genetic markers as means in the selection of highly productive animals. Since the genes: CSN3 (kappa-casein), PIT-1 (pituitary-specific transcription factor), PRL (prolactin), GH (somatotropin) are polymorphic and encode various proteins, the study of their influence on the productive traits of cattle is relevant. In this regard, the goal of the work is to determine the influence of complex genotypes of the studied genes on the milk productivity of first-calf cows of the Black-and-White breed bred in the collective farm-breeding plant «Kazminsky» in the Kochubeevsky district of the Stavropol Territory. The place of research is the Department of Genetics and Biotechnology, VNIIOK, a branch of the North Caucasian Federal National Research Center. This article presents the results of DNA genotyping of allelic polymorphism for the CSN3, PIT-1, PRL, GH genes using PCR-RFLP methods in first-calf cows of the Black-and-White breed. It was established that these genes in the studied sample are polymorphic. The frequency of occurrence of the desired CSN3B allele in the studied sample was 0.23. The presence of alleles PIT-1A and PIT-1B of the pituitary-specific transcription factor gene was noted with a frequency of occurrence of 0.52 and 0.48. A feature of the PRL gene polymorphism was the fairly high frequency of occurrence of the PRLA allele (0.60). In this study sample of dairy cattle, the frequency of occurrence of the desired GHL allele of the somatotropin gene was 0.62. All variants of complex genotypes were also identified and their relationship with milk productivity in black-and-white cows was noted. The study sample was dominated by animals carrying complex desirable genotypes, consisting of four and three marker alleles of three and two genes (CSN3AB/PIT-1BB/GHLV; CSN3AB/PIT1AB/GHLL or PIT-1AB/PRLAB/GHLV; PIT-1AA/GHLL ) - 46.7 %. Milk yield per lactation between groups of black-and-white first-calf cows with different complex genotypes ranged from 5839.14 to 8611.33 kg. The mass fraction of fat in milk ranged from 3.93 to 4.04 %, and protein from 2.99 to 3.14 %.

Correlation of Concentrations of Placental Growth Hormone Among Pregnant Females of MadhepuraDistrict of Bihar-India, during first/second and third trimester of their Pregnancy Phases, with the findings of U.S.G in terms of the Estimation of Placental Insufficiency or Sufficiency

Correlation of Concentrations of Placental Growth Hormone Among Pregnant Females of MadhepuraDistrict of Bihar-India, during first/second and third trimester of their Pregnancy Phases, with the findings of U.S.G in terms of the Estimation of Placental Insufficiency or Sufficiency

Complete genome sequence analysis of Pestalotiopsis microspora, a fungal pathogen causing kiwifruit postharvest rots

BackgroundThe postharvest rot of kiwifruit is one of the most devastating diseases affecting kiwifruit quality worldwide. However, the genomic basis and pathogenicity mechanisms of kiwifruit rot pathogens are lacking. Here we report the first whole genome sequence of Pestalotiopsis microspora, one of the main pathogens causing postharvest kiwifruit rot in China. The genome of strain KFRD-2 was sequenced, de novo assembled, and analyzed.ResultsThe genome of KFRD-2 was estimated to be approximately 50.31 Mb in size, with an overall GC content of 50.25%. Among 14,711 predicted genes, 14,423 (98.04%) exhibited significant matches to genes in the NCBI nr database. A phylogenetic analysis of 26 known pathogenic fungi, including P. microspora KFRD-2, based on conserved orthologous genes, revealed that KFRD-2’s closest evolutionary relationships were to Neopestalotiopsis spp. Among KFRD-2’s coding genes, 870 putative CAZy genes spanned six classes of CAZys, which play roles in degrading plant cell walls. Out of the 25 other plant pathogenic fungi, P. microspora possessed a greater number of CAZy genes than 22 and was especially enriched in GH and AA genes. A total of 845 transcription factors and 86 secondary metabolism gene clusters were predicted, representing various types. Furthermore, 28 effectors and 109 virulence-enhanced factors were identified using the PHI (pathogen host-interacting) database.ConclusionThis complete genome sequence analysis of the kiwifruit postharvest rot pathogen P. microspora enriches our understanding its disease pathogenesis and virulence. This study establishes a theoretical foundation for future investigations into the pathogenic mechanisms of P. microspora and the development of enhanced strategies for the efficient management of kiwifruit postharvest rots.

The effect of pregnancy-related hormones on hepatic transporters: studies with premenopausal human hepatocytes.

Pregnancy results in significant changes in drug pharmacokinetics (PK). While previous studies have elucidated the impact of pregnancy-related hormones (PRH) on mRNA or protein expression and activity of major hepatic metabolizing enzymes, their effect on hepatic drug transporters remains largely unexplored. Therefore, we investigated the effect of a cocktail of PRH on the mRNA expression and activity of hepatic transporters. Plated human hepatocytes (PHH) from 3 premenopausal donors were incubated, in triplicate, for 72h, with vehicle (DMSO < 0.01%), rifampin (10μM; positive control) or a cocktail of PRH consisting of estrone, estradiol, estriol, estetrol, progesterone, cortisol, testosterone, oxytocin, and placental growth hormone. The PRH concentrations replicated 0.1×, 1×, or 10× of the plasma concentrations of these hormones observed during each of the three trimesters of pregnancy. After treatment, mRNA expression (quantified by qPCR) of hepatic influx and efflux transporters as well as the activity of influx transporters was quantified (uptake of a selective substrate ± corresponding transporter inhibitor). The data were expressed relative to that in the control (vehicle) group. Significance was evaluated by ANOVA (followed by Dunn's multiple comparisons) or unpaired t-test when the within-lot data were analyzed, or repeated measures ANOVA (followed by Dunn's multiple comparisons) or paired t-test when data from all 3 lots were analyzed (p < 0.05). In general, a) PRH cocktails significantly induced transporter mRNA expression in the following order OAT2 ≈ NTCP ≈ OCT1 > OATP2B1 and repressed mRNA expression in the following order OATP1B3 > OATP1B1; b) these changes translated into significant induction of OAT2 (T1-T3) and NTCP (T2-T3, in only two lots) activity at the 1× PRH concentration. Compared with the influx transporters, the induction of mRNA expression of efflux transporters was modest, with mRNA expression of MRP2 and BSEP being induced the most. Once these data are verified through in vivo probe drug PK studies in pregnancy, they can be populated into physiologically based pharmacokinetic (PBPK) models to predict, for all trimesters of pregnancy, transporter-mediated clearance of any drug that is a substrate of the affected transporters.

Frequent Acquisition of Glycoside Hydrolase Family 32 (GH32) Genes from Bacteria via Horizontal Gene Transfer Drives Adaptation of Invertebrates to Diverse Sources of Food and Living Habitats.

Glycoside hydrolases (GHs, also called glycosidases) catalyze the hydrolysis of glycosidic bonds in polysaccharides. Numerous GH genes have been identified from various organisms and are classified into 188 families, abbreviated GH1 to GH188. Enzymes in the GH32 family hydrolyze fructans, which are present in approximately 15% of flowering plants and are widespread across microorganisms. GH32 genes are rarely found in animals, as fructans are not a typical carbohydrate source utilized in animals. Here, we report the discovery of 242 GH32 genes identified in 84 animal species, ranging from nematodes to crabs. Genetic analyses of these genes indicated that the GH32 genes in various animals were derived from different bacteria via multiple, independent horizontal gene transfer events. The GH32 genes in animals appear functional based on the highly conserved catalytic blades and triads in the active center despite the overall low (35-60%) sequence similarities among the predicted proteins. The acquisition of GH32 genes by animals may have a profound impact on sugar metabolism for the recipient organisms. Our results together with previous reports suggest that the acquired GH32 enzymes may not only serve as digestive enzymes, but also may serve as effectors for manipulating host plants, and as metabolic enzymes in the non-digestive tissues of certain animals. Our results provide a foundation for future studies on the significance of horizontally transferred GH32 genes in animals. The information reported here enriches our knowledge of horizontal gene transfer, GH32 functions, and animal-plant interactions, which may result in practical applications. For example, developing crops via targeted engineering that inhibits GH32 enzymes could aid in the plant's resistance to animal pests.

Effects of spectral on growth, physiology, and growth axis gene expression in Plectropomus leopardus

This study examined the effect of different spectral on the growth, feeding rate, digestion, and metabolism of Plectropomus leopardus in an industrial recirculating aquaculture system. All Plectropomus leopardus (wet weight 100 g ± 0.45 g) were kept in triplicate tanks for 60 days under six different spectral full visual (400 to 800 nm), blue (450 nm), green (530 nm), yellow (590 nm), red (630 nm) spectrum, and dark. After the experiment, fish were weighed and sampled to obtain haemolymph, brain, and hepatopancreas tissues, which were used to analyze biochemical parameters and gene expression. The findings indicated that the group exposed to blue light demonstrated substantially elevated feeding rate, weight gain, specific growth rate, and reduced feed conversion ratios and visceral-somatic indexes compared to the other groups (p < 0.05). The blue light and full spectrum groups had considerably increased levels of digestive, metabolic, and antioxidant enzyme activity compared to the other groups (p < 0.05). The expression levels of GH, GHR, PACA, ADCY, IGFI, IGFIR, and IGFBP growth axis genes in the brain and liver were significantly higher in the blue light group than in the other groups (p < 0.05). The results indicate that spectral impact the growth, feeding rate, digestion, and metabolism of P. leopardus. This study revealed distinct spectra that enhanced the growth rate and increased the weight gain from feeding. Furthermore, the optimal spectral composition for recycling aquaculture of P. leopardus was clarified, thereby providing theoretical references for designing lighting strategies in indoor recycling aquaculture systems tailored to P. leopardus.

Identification of the association of the GH, IGF-I and Pit-I gene polymorphism with growth traits in Saanen, Alpine and Boer goat breed

This study aims to determine an effect between GH, IGF-I, and Pit-I gene polymorphisms and growth traits such as body weight, heart girth, body length, height at wither, and chest width in Saanen, Alpine, and Boer goat breeds. The polymorphism was identified using the PCR-RFLP technique. GH/HaeIII gene polymorphism results identified two alleles (A and B) and two genotypes (AB and BB). A and B allele frequencies for Saanen, Alpine, and Boer goat breeds were found to be 0.438 and 0.562, 0.444 and 0.556, and 0.197 and 0.803, respectively. AB and BB genotype frequencies were found to be 0.876 and 0.124, 0.889 and 0.111, and 0.394 and 0.606, respectively. IGF-I/HaeIII gene polymorphism results identified two alleles (A and B) and three genotypes (AB, BB, and AA). A and B allele frequencies for the Saanen, Alpine, and Boer breeds were found to be 0.191 and 0.809, 0.173 and 0.827, and 0.182 and 0.818, respectively. The AB, BB, and AA genotype frequencies were found to be 0.315, 0.652, and 0.033 for Saanen, 0.247, 0.704, and 0.049 for Alpine, and 0.242, 0.697, and 0.061 for Boer, respectively. Regarding Pit-I/PstI gene polymorphism, T and C allele frequencies were determined as 0.921 and 0.079, 0.988 and 0.012, and 0.985 and 0.015 for Saanen, Alpine, and Boer breeds, respectively. TT and TC genotype frequencies were found to be 0.843 and 0.157, 0.975 and 0.025, and 0.970 and 0.030 in Saanen, Alpine, and Boer goats, respectively. An association was found between GH polymorphism and chest width in Saanen and Alpine goats and between body weight and heart girth in Boer goats. Additionally, an association was identified between IGF-I polymorphism and body weight in Alpine and chest width in Boer. There was also an association between Pit-I polymorphism and body weight in Alpine goats.

Differential peptide-dependent regulation of growth hormone (GH): A comparative analysis in pituitary cultures of reptiles, birds, and mammals

Growth hormone (GH) is a pituitary protein that exerts pleiotropic roles in vertebrates. The mechanisms regulating GH synthesis and secretion are finely controlled by hypothalamic neuropeptides and other factors. These processes have been considerably studied in mammals but are still poorly understood in other groups. To better understand the pituitary GH regulation during vertebrate phylogeny, we compared the effects of incubating several peptides on cultures of ex-vivo pituitary fragments obtained from representative specimens of reptiles (iguana), birds (chicken) and mammals (rat). The peptides used were: growth hormone-releasing hormone (GHRH), thyrotropin-releasing hormone (TRH), pituitary adenylate cyclase-activating polypeptide (PACAP), ghrelin, gonadotropin-releasing hormone (GnRH), and somatostatin (SST). In rat pituitary cultures, GH secretion was stimulated by GHRH and TRH, while gh mRNA expression was increased by GHRH and PACAP. In the case of chicken pituitaries, GH release was promoted by GHRH, ghrelin, PACAP, and GnRH, although the latter two had a dual effect since at a shorter incubation time they decreased GH secretion; in turn, gh mRNA expression was significantly stimulated by TRH, PACAP, and GnRH. The most intense effects were observed in iguana pituitary cultures, where GH secretion was significantly augmented by GHRH, PACAP, TRH, ghrelin, and GnRH; while gh mRNA expression was stimulated by GHRH, TRH, and PACAP, but inhibited by ghrelin and SST. Also, in the three species, SST was able to block the GHRH-stimulated GH release. Furthermore, it was found that the expression of Pou1f1 mRNA was increased with greater potency by GHRH and PACAP in the iguana, than in chicken or rat pituitary cultures. Additionally, in-silico analysis of the gh gene promoter structures in the three species showed that the reptilian promoter has more Pit-1 consensus binding sites than their avian and mammalian counterparts. Taken together, results demonstrate that pituitary peptide-mediated GH regulatory mechanisms are differentially controlled along vertebrate evolution.

Experimental Autoimmune Encephalomyelitis Influences GH-Axis in Female Rats.

Inflammation, demyelination, and axonal damage to the central nervous system (CNS) are the hallmarks of multiple sclerosis (MS) and its representative animal model, experimental autoimmune encephalomyelitis (EAE). There is scientific evidence for the involvement of growth hormone (GH) in autoimmune regulation. Previous data on the relationship between the GH/insulin like growth factor-1 (IGF-1) axis and MS/EAE are inconclusive; therefore, the aim of our study was to investigate the changes in the GH axis during acute monophasic EAE. The results show that the gene expression of Ghrh and Sst in the hypothalamus does not change, except for Npy and Agrp, while at the pituitary level the Gh, Ghrhr and Ghr genes are upregulated. Interestingly, the cell volume of somatotropic cells in the pituitary gland remains unchanged at the peak of the disease. We found elevated serum GH levels in association with low IGF-1 concentration and downregulated Ghr and Igf1r expression in the liver, indicating a condition resembling GH resistance. This is likely due to inadequate nutrient intake at the peak of the disease when inflammation in the CNS is greatest. Considering that GH secretion is finely regulated by numerous central and peripheral signals, the involvement of the GH/IGF-1 axis in MS/EAE should be thoroughly investigated for possible future therapeutic strategies, especially with a view to improving EAE disease.

Angiopoietin-like protein 4 induces growth hormone variant secretion and aggravates insulin resistance during pregnancy, linking obesity to gestational diabetes mellitus.

Angiopoietin-like protein 4 (ANGPTL4) is a secretory glycoprotein involved in regulating glucose homeostasis in non-pregnant subjects. However, its role in glucose metabolism during pregnancy and the pathophysiology of gestational diabetes mellitus (GDM) remains elusive. Thus, this study aimed to clarify the relationship between ANGPTL4 and GDM and investigate the pathophysiology of placental ANGPTL4 in glucose metabolism. We investigated this issue using blood and placenta samples in 957 pregnant women, the human 3A-sub-E trophoblast cell line, and the L6 skeletal muscle cell line. We found that ANGPTL4 expression in the placenta was higher in obese pregnant women than in lean controls. Palmitic acid significantly induced ANGPTL4 expression in trophoblast cells in a dose-response manner. ANGPTL4 overexpression in trophoblast cells resulted in endoplasmic reticulum (ER) stress, which stimulated the expression and secretion of growth hormone-variant (GH2) but not human placental lactogen. In L6 skeletal muscle cells, soluble ANGPTL4 suppressed insulin-mediated glucose uptake through the epidermal growth factor receptor (EGFR)/extracellular signal-regulated kinases 1/2 (ERK 1/2) pathways. In pregnant women, plasma ANGPTL4 concentrations in the first trimester predicted the incidence of GDM and were positively associated with BMI, plasma triglyceride, and plasma GH2 in the first trimester. However, they were negatively associated with insulin sensitivity index ISI0,120 in the second trimester. Overall, placental ANGPTL4 is induced by obesity and is involved in the pathophysiology of GDM via the induction of ER stress and GH2 secretion. Soluble ANGPTL4 can lead to insulin resistance in skeletal muscle cells and is an early biomarker for predicting GDM.

The Effect of Metformin Treatment on Disease Control in Patients with Acromegaly.

The increase in portal insulin levels has been shown to upregulate growth hormone receptor expression in the liver, leading to increased insulin-like growth hormone- 1 levels. Metformin inhibits hepatic gluconeogenesis and reduces fasting insulin. We evaluated the effect of metformin treatment in patients with acromegaly on growth hormone, insulin-like growth hormone-1, and pituitary adenoma size. Patients who were followed up with the diagnosis of acromegaly in Istanbul University- Cerrahpaşa, Cerrahpaşa Medical Faculty were evaluated. The patients were divided into three groups after pituitary adenectomy as those who received somatostatin receptor ligand and metformin treatment (group A), somatostatin receptor ligand treatment only (group B), and those who received metformin treatment only (group C). Groups A and B were compared with each other, and patients in group C were compared among themselves. While the median insulin-like growth factor-1 level decreased to 170 ng/ml in Group A after the treatment, the median insulin-like growth factor-1 level decreased to 229 ng/ml in Group B, and a statistically significant difference was found between the two groups (p =0.020). There was no significant difference in post-treatment growth hormone levels and residual adenoma sizes between groups A and B (p >0.005). In group C, there was no significant difference in growth hormone values pre-and post-metformin treatment (p =0.078); however, the median insulin-like growth factor-1 level decreased from 205 ng/ml to 168 ng/ml during metformin treatment and was found to be statistically significant (p =0.027). Due to the effect of metformin treatment on insulin-like growth factor-1 values in patients with acromegaly, it can be used in disease control, as well as diabetes treatment.

Genotoxic Effects of Cassava Effluent on the Expression of Selected Genes in the African Catfish, Clarias gariepinus

Aim: A cause for worry is the wastewater that is released into the environment or public sewers without any sort of purpose during the processing of Manihot esculenta Crantz. Fish and other aquatic species may suffer negative consequences if wastewater is discharged into streams and rivers, either directly or indirectly. This study was conducted to examine the effects of cassava effluents on gene expression in the African catfish (Clarias gariepinus). Methodology: C. gariepinus juveniles were exposed to 0.1, 0.5, 1.0 and 1.5 % concentrations of cassava effluent, respectively. The subsequent tissue extraction, RNA isolation, cDNA synthesis and electrophoresis analysis were all done following standard procedures. Results: From the results obtained, there were varying levels of upregulation in the expression levels of all the nine genes assessed: IL-1β, CYPIIA, HSP70, DMRTI, HSD17B, FOX12, MEL1C, CAMKIIg and GH genes. Statistical analysis to compare the expression levels of the genes at the different concentrations with their corresponding control experiments showed that the upregulation of only two genes, (HSD17B and GH), upon exposure to cassava effluents were not significant (p &gt;0.05) at any concentration. The upregulation of the seven other genes is an indication that the cassava effluents exerted adverse impacts on the physiology of C. gariepinus. Conclusion: It is therefore recommended that cassava effluents be properly treated before being discharged into the aquatic environment.

Early nutritional programming in sterlet sturgeon (Acipenser ruthenus) with dietary soybean meal: Assessment of growth performance, body composition, and expression of GH, IGF-I, and Ghrelin genes.

This study was performed to assess the impacts of introducing diets containing different levels of soybean meal (SBM) to sterlet sturgeon (Acipenser ruthenus) larvae on growth performance, body composition, and molecular responses in the juvenile stage. The sterlet larvae (57.68 ± 0.66 mg) were weaned onto the formulated diets as follows: a control diet containing 60% fishmeal (FM), and three experimental diets with replacement levels of 15% (SBM15), 30% (SBM30), and 45% (SBM45) of FM with SBM. Then, a total of 260 fish (initial weight: 323.33 ± 11.76 mg) were fed the four different diets for 28 days in triplicates (phase 1, nutritional programming, NP). All treatments were then fed with the FM diet in phase 2 (common phase), and in phase 3 (challenge phase), all experimental groups (6.14 ± 0.08 g) were transitioned to SBM45 for 28 days. At the end of phases 1 and 2, growth performance showed no significant differences among the groups (P > 0.05), while significantly improved in SBM45 than the control at the end of phase 3 (P < 0.05). No significant differences were found among the groups in any phases for whole body composition (P > 0.05). Additionally, the total saturated fatty acids were significantly higher in SBM-based diets than FM at the end of phase 3 (P < 0.05). The mRNA of GH, IGF-I was significantly affected by variation of FM replacement level (P < 0.05). The expression level of Ghrelin was up-regulated in fish fed SBM at the end of phase 3 (P < 0.05). Our findings revealed that NP can positively enhance the adaptation of juvenile sterlet sturgeon to 45% SBM when exposed to the same diets at the larval stage. Further research is being carried out to provide valuable insights into the underlying mechanisms of digestive performance for this species.

Quantitative characteristics and growth hormone gene diversity of thin-tailed sheep in Sitinjau Laut, Kerinci Regency

&lt;p class="MDPI17abstract"&gt;&lt;strong&gt;&lt;span lang="EN-US"&gt;Objective:&lt;/span&gt;&lt;/strong&gt;&lt;span lang="EN-US"&gt; This study aims to evaluate the &lt;/span&gt;&lt;span lang="IN"&gt;quantitative characteristics and growth &lt;/span&gt;&lt;span lang="EN-US"&gt;h&lt;/span&gt;&lt;span lang="IN"&gt;ormone gene&lt;/span&gt;&lt;span lang="EN-US"&gt; diversity of thin-tailed sheep&lt;/span&gt;&lt;span lang="IN"&gt; in Sitinjau Laut&lt;/span&gt;&lt;span lang="EN-US"&gt;,&lt;/span&gt;&lt;span lang="IN"&gt; Kerinci Regency&lt;/span&gt;&lt;span lang="EN-US"&gt;.&lt;/span&gt;&lt;/p&gt;&lt;p class="MDPI17abstract"&gt;&lt;strong&gt;&lt;span lang="EN-US"&gt;Methods:&lt;/span&gt;&lt;/strong&gt;&lt;span lang="EN-US"&gt; The research method used 60 thin-tailed sheep and 60 samples of thin-tailed sheep's blood. The phenotypes observed included: body weight, weight gain, body measurements, and thin-tailed sheep blood samples. The GH gene was identified using the PCR-RFLP method with the Msp1 restriction enzyme. Data analysis included t-test, t&lt;sup&gt;2&lt;/sup&gt;-hotelling, principal component analysis, and allele genotype frequencies.&lt;/span&gt;&lt;/p&gt;&lt;p class="MDPI17abstract"&gt;&lt;strong&gt;&lt;span lang="EN-US"&gt;Results:&lt;/span&gt;&lt;/strong&gt;&lt;span lang="EN-US"&gt; The results showed that body weight, body weight gain, and sizes of male thin-tailed sheep were significantly different (P&amp;lt;0.05) higher than females. The analysis results on the GH|Msp1 gene locus of thin-tailed sheep were monomorphic with one type of allele, namely ++. &lt;/span&gt;&lt;/p&gt;&lt;p&gt;&lt;strong&gt;&lt;span lang="EN-US"&gt;Conclusions:&lt;/span&gt;&lt;/strong&gt;&lt;span lang="EN-US"&gt; The average body weight, weight gain, and body measurements of male thin-tail sheep were higher than that of females. The body size characteristic of male and female thin-tailed sheep is the chest circumference, while the body shape characteristic of male and female thin-tailed sheep is the chest depth. The fragmentation of the GH|Msp1 gene in thin-tailed sheep is monomorphic.&lt;/span&gt;&lt;/p&gt;

Screening of GHSR, GHRHR, GH1 genes in isolated growth hormone deficiency disease in Egyptian patients

Abstract Background Isolated growth hormone deficiency (IGHD) is a hereditary disorder that causes significant short stature. GHD has a reported incidence of 1/4000–1/10,000 births. It is caused by mutations in the major somatotroph axis genes, involving GH1, codes for growth hormone, GHSR, and GHRHR, codes for growth hormone secretagogue receptor and growth hormone-releasing hormone receptor, respectively. Aims of the study The present study aims to examine the clinical phenotype and investigate the genetic etiology of ten Egyptian patients with type I isolated growth hormone insufficiency. Patients and methods Patients recruited for the study were clinically diagnosed by two provocation tests and were subjected to a thorough history, clinical examination, and anthropometric measurements. Sanger sequencing and mutational analysis of the three genes, GH1, GHSR, and GHRHR, was our approach, performed in all enrolled IGHD patients. The variants identified were analyzed using the biological, population, sequence variants, and clinical genetics databases. Prediction of the pathogenicity of the novel variants was done by in silico prediction tools following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results Sanger sequencing revealed a previously reported pathogenic mutation (NM_000823.4: c.1069C &gt; T; p.Arg357Cys) in the GHRHR gene in one patient and a novel frameshift variant (NM_198407.2: c.1043dup; Ser349Leu fs*6) in the GHSR gene in another patient. This is the fourth report highlighting the autosomal dominant inheritance of the GHSR mutation as a cause of isolated growth hormone deficiency. A number of previously reported variants, but of rare frequency, were identified in this study. In our IGHD cases, 90% of the patients were underweight, 50% had anemia, and 80% showed hypovitaminosis D. Conclusion Our findings broaden the mutational spectrum underlying the IGHD in Egyptian patients and point out the importance of mutation screening of the GHSR and GHRHR genes. This study also acknowledges the autosomal dominant mode of inheritance of the GHSR mutation as a cause for dwarfism.

Effects of Somatotropic Axis Gene Polymorphisms on Milk Yields in Simmental Cattle

Due to the increasing world population, scientists aim to obtain high-yield products using new techniques and methods to meet needs in the fields of food, agriculture, and livestock. It is very important to selected the candidate genes and markers correctly, especially in the QTL and MAS techniques in livestock. Somatotropic axis genes affect yield traits, growth, reproduction, and milk production in cattle. In the study, we determined GH/AluI and IGFI/SnaBI gene polymorphisms using the PCR-RFLP technique in DNA samples obtained from 70 Simmental cattle. The allele frequencies of the genes were in the same proportion as 0.62 and 0.38, L and V for the GH gene and T and C for the IGFI gene. There was no significant relationship between the polymorphic genotypes of the genes we examined and lactation milk yields, 305-day milk yields, daily milk yields, and lactation periods of Simmental cattle. The probability of using bGH/AluI and IGFI/SnaBI genetic variations as markers in association studies with milk yield in cattle is extremely low.&#x0D; Keywords: Axis genes; RFLP; MAS; Simmental; milk yield

The association between plasma angiopoietin-like protein 4, glucose and lipid metabolism during pregnancy, placental function, and risk of delivering large-for-gestational-age neonates

BackgroundLarge-for-gestational-age (LGA) neonates have increased risk of adverse pregnancy outcomes and adult metabolic diseases. We aimed to investigate the relationship between plasma angiopoietin-like protein 4 (ANGPTL4), a protein involved in lipid and glucose metabolism during pregnancy, placental function, growth factors, and the risk of LGA. MethodsWe conducted a prospective cohort study and recruited women with singleton pregnancies at the National Taiwan University Hospital between 2013 and 2018. First trimester maternal plasma ANGPTL4 concentrations were measured. ResultsAmong 353 pregnant women recruited, the LGA group had higher first trimester plasma ANGPTL4 concentrations than the appropriate-for-gestational-age group. Plasma ANGPTL4 was associated with hemoglobin A1c, post-load plasma glucose, plasma triglyceride, plasma free fatty acid concentrations, plasma growth hormone variant (GH-V), and birth weight, but was not associated with cord blood growth factors. After adjusting for age, body mass index, hemoglobin A1c, and plasma triglyceride concentrations, plasma ANGPTL4 concentrations were significantly associated with LGA risk, and its predictive performance, as measured by the area under the receiver operating characteristic curve, outperformed traditional risk factors for LGA. ConclusionsPlasma ANGPTL4 is associated with glucose and lipid metabolism during pregnancy, plasma GH-V, and birth weight, and is an early biomarker for predicting the risk of LGA.