GH Gene Research Articles

Genetic markers in sheep breeding

The priority direction in developing domestic sheep breeding is the creation of new and improved breeding forms that combine high meat and wool productivity rates with good adaptive qualities to breeding conditions. In Russia, 404.2 thousand heads of coarse-wool sheep breeds and 21.2 thousand heads of semi-coarse-wool sheep are concentrated on breeding farms. Compared to 2000, the number of breeding animals increased by 5.0 times, while the yield of lambs for slaughter per 100 breeding queens increased by 5.7 times. One way to increase the selection and breeding work with breeds is to search and use genetic markers of productivity and vitality. The work aimed to summarise and analyse information about the genetic polymorphism of genes associated with traits of productivity and disease resistance in different breeds of sheep. The results of studies of polymorphic variants of genes related to the growth energy of young animals, wool quality and meat productivity in sheep are presented. The calpastatin (CAST) gene is described, which is associated with meat productivity and tenderness of meat the KRT (keratins) gene - with wool productivity and wool quality, the growth hormone gene GH and the differential growth factor gene GDF9 - with the regulation of growth and development, reproductive qualities and meat production, sheep productivity. In most studies, the predominant genotype in all breeds is CASTMM. The frequency of genotypes for the KRT and GH genes in breeds of different directions of productivity varies significantly. The relationship of genotypes CAST, GН, and GDF9 with economically valuable traits is described, making it possible to consider their genetic markers.

Genetic Diversity Analysis of Exon-2 Growth Hormone (GH) Gene in Crossbred Chicken (Sentul X Arab) using PCR-RFLP Technique

The research aims to analyze the genetic diversity of the GH gene using the PCR-RFLP technique. Fifty blood samples were collected from crossed Sentul and Arab Chickens aged three months. DNA was extracted from whole blood samples, and its quantity was evaluated by bio-drop technique. Extracted DNA was amplified for gene GH using a PCR machine. The PCR product was restricted by MspI (C↓CGG) and Hae-III (GG↓CC) enzymes for identifying the fragment length diversity. The variables observed in this study were DNA quantitative analysis, the genotype, and alleles of the obtained genotype. The result shows the extracted DNA is of good quality because it has values >1.8 and <2.0, which means there’s no contamination in the DNA. GH gene was amplified with primers of 519 bp and showed that a DNA band matched the target in the specified primer design. Analysis of Genetic Diversity shows the monomorphic GH gene in this research. The genotype obtained at the GH-HaeIII locus is AA, and at the GH-MspI locus is TT. Both enzymes weren’t restricted to these amplification design sites.

Oregano Leaf Extract Dietary Administration Modulates Performance, Redox Status, Intestinal Health, and Expression of Some Related Genes of Nile Tilapia (Oreochromis niloticus L.)

Abstract The main objective of the current trial was to evaluate the beneficial influences of Origanum vulgare leaf extract (OVLE) on growth, some blood indices, redox status, and the expression of some growth and immune-related genes. Three thousand seven hundred and eighty Nile tilapia fingerlings were allocated to six equal groups. The first group served as a control and received a basal diet, while the other five groups were fed diets containing graded amounts of OVLE (0.1, 0.2, 0.3, 0.4, and 0.5%, respectively) and defined as OVLE0.1, OVLE0.2, OVLE0.3, OVLE0.4, and OVLE0.5 for 98 days. Growth performance and feed efficiency parameters were significantly improved in OVLE0.4 and OVLE0.5 groups compared with the control group. The hematological indices, specifically hemoglobin, red blood cell, and white blood cell count were significantly increased in the fish group fed a 4% OVLE-supplemented diet compared to other groups. Fish fed higher dietary inclusion levels of OVLE significantly increased total protein and albumin concentrations compared to other experimental groups. The OVLE0.4 and OVLE0.5 supplemented groups promoted innate immune response and phagocytic activity and stimulated the lipase enzyme activity of Nile tilapia. All estimated redox markers were significantly improved in the fish groups that received 4 or 5% OVLE compared with the control and other OVLE groups. The fish groups fed higher levels of OVLE significantly upregulated the expression of GH, IL-8, and IL-1β genes and downregulated the expression of the Hsp70 gene. Furthermore, the intestinal histological features demonstrated normal structure in all OVLE-administered fish groups, with improved intestinal villus length compared to the untreated group. Finally, it could be concluded that including OVLE in the Nile tilapia diet at higher levels (0.4 up to 0.5%) could improve performance and general health status.

Polymorphic Analysis of the GH Gene (Exon 3 and 4) and its Association with Growth Traits in Pakistani Quail (Coturnix japonica PK)

Polymorphic Analysis of the GH Gene (Exon 3 and 4) and its Association with Growth Traits in Pakistani Quail (Coturnix japonica PK)

Relationship Between Growth Hormone Gene Polymorphism with Milk Production and Its Components in Black Iraqi Goat

Local black goat are raised for the purpose of milk production. The goal of the current study was to identify the growth hormone gene's single nucleotide polymorphism (SNPS). Additionally, the effect of the GH gene SNP on the milk qualities of Iraqi black goat was evaluated. DNA was extracted from blood samples of 28 goat. A segment with a length of 330 bp in the third intron and the fourth exon of the GH gene was analyzed. Bioinformatics software was used to analyze the results. The results showed the presence of three genotypes (TT, TC, CC) at position 263 of the studied plot with a frequency of 0.36, 0.21, and 0.43, respectively. The local breed was characterized by a decrease in observed heterozygosity (21.43%). However, the expected heterozygosity was 50.65%. Low heterozygosity may indicate the presence of inbreeding within the same herd. Haplotypes network revealed a genetic relationship between the local Iraqi goat and the Egyptian goat. As well as the existence of a genetic relationship at a lower level with the Indian goats. From Tajima's D test and Fu's Fs (1.547 and 1.428), the results led to a rise in inbreeding. In milk production, energy, and the amounts of protein. The analysis of the data using bioinformatics tools predicted the effects of identified the genotypes in which the amino acid was not altered, and this is where the mutation was found. There is a relationship between the genetic polymorphism of the growth hormone gene and the production of milk and its components. The CC genotype was superior in milk production, energy, and the amounts of protein and fat over the TC and CC combinations.

Associations of CAST, GH gene polymorphism in young sheep with a blood type of ? Charolais + ? Kalmyk kurdyuchnaya with measurements of body articles and indices of physique

To increase the production of meat productivity, it is necessary to improve the genetic resources of sheep. The purpose of this work was to establish the allelic spectrum of the calpastatin (CAST) and somatotropin (GH) genes, and their associations with meat productivity in young animals of mixed stock with a bloodline of ? Charolais + ? Kalmyk chicken and to identify the effects of polymorphism of gene markers on the exterior parameters of young animals. The object of the study is the repair young sheep reared in the farm "Arl" of the Yashkul district of the Republic of Kalmykia. The PCR-PDRF method determined the allelic spectrum of genes: calpastatin (CAST), somatotropin (GH), in young hybrids with a blood type of ? Charolais + ? Kalmyk chicken. The superiority of the CASTM allele (0.78) over the frequency of occurrence of the selectively significant CASTN allele (0.22) was noted in the calpastatin gene in crossbreed livestock. According to the growth hormone gene, molecular genetic analysis showed that the frequency of occurrence of the GHA allele in young mixed sheep was 0.88, and the frequency of occurrence of the selectively significant GHB allele was 0.12. A comparative analysis of the live weight of animals with different genotypes showed that sheep and sheep carriers of heterozygous CASTMN and GHAB genotypes have higher live weight indicators than their peers with homozygous CASTMM and GHAA genotypes. Measurements of articles of exterior and indices of physique depending on genotypes are described, since their use allows breeders to determine the type of constitution, individual characteristics, degree and proportionality of the development of the organism, age variability, condition and ability to a particular productivity.

FOXO1 regulates expression of Neurod4 in the pituitary gland

Pituitary gland function is regulated by the activity of various transcription factors that control cell fate decisions leading to cellular differentiation and hormone production. FOXO1 is necessary for normal somatotrope differentiation and function. Recent in vivo data implicate FOXO1 in the regulation of genes important for somatotrope differentiation including Gh1, Neurod4, and Pou1f1. In the current study, the somatotrope-like cell line GH3 was treated with a FOXO1 inhibitor, resulting in significant reduction in Neurod4 and Gh1 expression. Consistent with these findings, CRISPR/Cas9-mediated deletion of Foxo1 in GH3 cells significantly reduced expression of Gh1 and Neurod4. Chromatin immunoprecipitation sequencing identifies novel FOXO1 binding sites associated with the Neurod4, Gh1, and Pou1f1 genes. The FOXO1 binding site in the Neurod4 gene exhibits enhancer activity in somatotrope-like cells but not in gonadotrope-like cells. These data strongly suggest FOXO1 directly contributes to the transcriptional control of genes important for somatotrope differentiation.

Increasing the productive potential of large and small cattle breed resources in the South of Russia based on modern breeding methods

The results of the genetic characteristics research of large and small cattle populations grown in the Southern Russia are stated. Breed-specific DNA patterns have been identified in three of the most common cattle breeds of meat productivity in arid conditions. The milk productivity of Holstein cows of different breeding lines has been studied. It was found that increasing the frequency of animals of Vis Back Ideal and Reflection Sovering lines in the parent pairs could be able to increase the level of milk productivity of offspring and improve the quality indicators of dairy raw materials. The adaptive abilities and milk productivity of imported foreign Holstein cows depending on their origin were estimated. In comparison with Australian and Danish Holstein cows, American and German analogues have a higher level of milk productivity. However Australian and Danish animals have a more flexible adaptive capacity. As a result of the comparative study of the economic and biological characteristics of two generations of Aberdeen-Angus cattle (parental foreign generation, and the first generation - obtained under breeding conditions in Southern Russia), tendencies to increase productive values are revealed. The features of the meat productivity formation in Kalmyk steers different exterior and constitutional types are investigated. It was found that the Kalmyk steers of the tall body type have a higher meat productivity compared with their analogues of medium and compact body types. However, the beef of compact steers has a higher fat percentage, more attractive taste characteristics, culinary and technological indices. The features of polymorphism of CAST, GH, GDF9, CLPG, FABP4 and MC4R genes in populations of sheep of different breeds grown in the Republic of Kalmykia, Volgograd and Rostov regions, Kabardino-Balkaria Republic were also studied. As a promising method of early diagnosis of presence economically useful traits in sheep during ontogenesis, the effectiveness of DNA analysis in young lambs and the further selection of animals with desirable genotypes according to these genes were justified.

Analysis of allelic variants in genes associated with meat productivity in regionalized small cattle breeds

The purpose of the research was to study the polymorphism of allelic variants of genes associated with high meat productivity for further selection of parental pairs using genetic methods. Genotyping of the Dagestan mountain sheep breeds (broodstock and rams) was carried out using a polymerase chain reaction. Genotyping was carried out for the following genes: CAST, GH, GDF9 on a Tertsik thermal cycler. Analysis of the results of PCR carried out with samples of sires of the Dagestan rock breed indicates that the GH gene polymorphism is represented by the A allele, with a high (0.87) and allele B, with a low (0.13) frequency of occurrence. The GDF9 gene polymorphism is represented by the GDF9G allele with a high (0.82) and the GDF9A allele with a low (0.18) frequency of occurrence. The distribution of homozygous genotype GHAA and heterozygous GHAB reached 84% and 16%, respectively. At the same time, the homozygous GHBB* genotype was absent in the studied sample. As a result of the research, new knowledge was obtained on biodiversity and forms of associations of polymorphism of the genes calpastatin, somatotropin, differential growth factor; breed-specific, population-specific features of the allelic spectrum of the CAST, GH, GDF9 genes in sheep of the Dagestan mountain sheep breed were established.

Dietary effects of microalga Tetraselmis suecica on growth, antioxidant-immune activity, inflammation cytokines,and resistance of Nile tilapia fingerlings to Aeromonas sobria infection.

The dietary effects of the green microalga Tetraselmis suecica (TS) on the growth, digestive enzymes, immune and antioxidant responses, genes expression,and disease resistance of Nile tilapia (Oreochromis niloticus) fingerlings were investigated. This microalga was mixed with the diet'ingredients at doses of 0.0 (the control), 5, 10, 15,and 20 g/kg diet and then fed to fish daily for 84 days. After the feeding trial, fish were experimentally challenged with Aeromonas sobria, infection and fish mortalities were recorded for another 10days. Dietary TS significantly (p < 0.05) enhanced growth, digestive enzymes activities,and blood proteins, particularly at the level of 15 g/kg diet. Feeding the fish on 15 TS/kg feed exhibited highest mRNA expressions of GH and IGF-1 genes as well as SOD, CAT,and GPx genes compared to other TS groups. Moreover, highest levels of hepatic antioxidant and immune indices were found in the treatment of 15 g TS/kg feed. Significant downregulation of IL-1β and IL-8 genes expression and significant upregulation of IL-10 gene expression were observed in TS-fed fish, principally in fish groups fed on 15-20 g TS/kg feed. Conversely, hepatic malondialdehyde levels, blood glucose,and the activities of transaminases (ALT and AST) were significantly (p < 0.05) decreased in fish fed with 15-20 g TS/kg diet. Serum bactericidal activity against A. sobria was significantly higher in TS-fed fish groups, and its highest levels were found in treatments of 15-20 g/kg diet. Of interest, the survival rates of fish groups fed diets with 10-20 g TS/kg feed were higher after the challenge with A. sobria infection than the control group. Accordingly, we can conclude that supplementing fish diets with a 15 g TS/kg diet enhanced the growth, antioxidant and immune activities,and resistance of Nile tilapia fingerlings to possible A. sobria infection.

Differential biomarker expression in heart failure patients with and without mitral regurgitation: Insights from BIOSTAT-CHF

BackgroundMitral regurgitation (MR) frequently coexists with heart failure (HF). ObjectivesTo better understand potential pathophysiological differences between patients with HF with or without moderate-severe MR, we compared differentially expressed circulating biomarkers between these two groups. MethodsThe Olink Proteomics® Multiplex Cardiovascular (CVD) -II, CVD-III, Immune Response and Oncology-II panels of 363 unique proteins from different pathophysiological domains were used to investigate the biomarker profiles of HF patients from index and validation cohorts of the BIOSTAT-CHF study stratified according to the presence of moderate-to-severe MR or no-mild MR. ResultsThe index cohort included 888 patients (46%) with moderate-to-severe MR and 1029 (54%) with no-mild MR at baseline. The validation cohort included 522 patients (33%) with moderate-to-severe MR and 1076 (66%) with no-mild MR at baseline. Compared to patients with no-mild MR, those with moderate-to-severe MR had lower body mass index, higher comorbidity burden, signs and symptoms of more severe HF, lower systolic blood pressure, and larger left atrial and ventricular dimensions, in both cohorts. NT-proBNP, CA125, fibroblast growth factor 23 (FGF23) and growth hormone 1 (GH1) were up-regulated, whereas leptin (LEP) was down-regulated in patients with moderate-severe MR versus no-mild MR, in both index and validation cohorts. ConclusionCirculating biomarkers differently expressed in HF patients with moderate-severe MR versus no-mild MR were related to congestion, lipid and mineral metabolism and oxidative stress. These findings may be of value for the development of novel treatment targets in HF patients with MR.

Development of a recombinant protein-based ELISA for detection of antibodies against bovine herpesvirus 6 (BoHV6).

Bovine herpesvirus 6 (BoHV6) belongs to the Herpesviridae family, Gammaherpesvirinae subfamily and Macavirus genus. It is common in cattle, but was also detected in American bison (Bison bison) and water buffalo (Bubalus bubalis). The aim of the experiment was to develop an ELISA for serological examination of cattle sera for the presence of anti-BoHV6 specific antibodies. Viral DNA from a BoHV6-positive cow was amplified by qPCR and the resulting fragments of the gB and gH genes encoding glycoproteins B and H (gB and gH) were cloned into the pLATE52 vector to express recombinant gB (rgB) and gH (rgH) in Rosetta (DE3) E. coli. The expressed recombinant proteins were used as antigens in the developed ELISA. The proteins expressed had the expected molecular weight. A total of 143 sera were examined, and 141 of them were positive, according to the chosen cut-off values of 9% and 10% for the sample-to-positive ratios of the rgB and rgH antigens, respectively. The rgB and rgH recombinant antigens of BoHV6 were successfully expressed in E. coli and successfully used in a newly developed ELISA.

Study some Genetic Variance and Breeding Value on Productive Performance for Local Chicken Differ in Polymorphism of Growth Hormone Gene

To fix and detect some value of genetic selection parameters for hens of local chicken differ in growth hormone GH gene polymorphisms, PCR-RFLP technique used with MSP restriction enzyme, three genotype found as AA the wild, AB the heterosis and the mutant BB. Results of some genetic analysis indicating that based on breeding value BV for AA genotype was the highest one 79.913 for body weight at sexual maturity and 1.736 for average age at sexual maturity and 4.373, 5.894 and 0. 438 for average egg product at 100 days and average egg weight at 27 and 34 weeks respectively for the seam AA hens’ genotype. The lowest value for dominant deviation DD was 0.298 for traits of average first egg weight, for body weight at sexual maturity was – 6.659 and – 5.58 for average age at sexual maturity and 0.012 for average egg weight at 20 weeks and 0.042 for average egg weight at 34 weeks for hens with BB genotype. AB genotype was low in trait for average egg weight at 27 and 34 weeks with value of 8.044 and – 0.08 respectively. In conclusion molecular procedure result indicating that depending on some molecular genetic parameters RFLP for such gene of relation with productive performances and BV includes some genetic variances as DD, DV and VA and GV are good tools used in selection programs for local hen’s chicken either if their genotype is with one or two copies of allele A in order to achieve the best genetic group in the way of improving production efficiency for Iraqi local chickens.

Milk-y Way: the impact of single-nucleotide polymorphisms on milk production traits in Kilis dairy goats.

This study aimed to investigate the impact of single-nucleotide polymorphisms (SNPs) on milk production traits in Kilis dairy goats by analyzing the genotypes of POU1F1, PRLR, -Lg, GH1, and GH2 genes and their association with lactation milk yield (LMY), lactation length (LL) and average daily milk yield (ADMY). Blood samples were collected from 227 goats, and genotyping was performed using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). The results revealed that the frequencies of the genotypes varied among the genes. The polymorphisms were found to be significantly linked with milk production traits. These findings suggest that SNPs of POU1F1/AluI, PRLR/RsaI and -Lg/SacII are significantly associated with LMY and that the POU1F1-TC genotype, PRLR-TT genotype and -Lg-AB genotype are associated with higher LMY and ADMY. Additionally, the POU1F1-TC genotype was found to have a longer LL. However, no significant association was found between the GH1 and GH2 genotypes and LMY, LL and ADMY. Overall, this study provides valuable insights into the genetic factors influencing milk production traits in Kilis dairy goats, which can be utilized for the selection of high-yielding animals in breeding programs.

Impacts of high-dose riboflavin on cytotoxicity, antioxidant, growth, reproductive gene expressions, and genotoxicity in the rainbow trout gonadal cells

Riboflavin (vitamin B2 found in food) is a precursor of flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), which study as coenzymes for a variety of cellular processes including biosynthesis, homocysteine metabolism, detoxification, and various oxidation and reduction reactions. Although studies on the symptoms resulting from riboflavin deficiency are intense, studies on the effects of high doses of riboflavin are almost absent. This report aimed to examine the actions of riboflavin on cell viability, the transcriptional expressions of antioxidant enzyme (gsr and gpx1a), growth (gh1, igf1, and igf2), the reproductive (bol) genes and DNA damage in the rainbow trout gonad cells (RTG-2) for 48 h. All concentrations of riboflavin (3.125, 6.25, 12.5, 25, 50, and 100 μM) significantly reduced the RTG-2 cell viability. Riboflavin (LD50: 12.5 μM) significantly downregulated the transcriptional expressions of gpx1a, igf1, and bol genes, while it non-significantly upregulated or downregulated the transcriptional expression of gsr, igf2, and gh1 genes in the RTG-2 cells in comparison to the control group for 48 h. The comet assay demonstrated that riboflavin significantly raised tail DNA% >10% DMSO (positive control). Based on the outcomes, high doses of riboflavin exhibit the potential to have a role in cellular mechanisms, including especially reproduction, DNA damage, and cell death.

Analysis of polymorphisms in genes associated with milk productivity in red steppe and Caucasian brown cow breeds in two natural‐climate zones (mountains and plain) of Dagestan, Russia

Aim. The unique gene pool of indigenous breeds in the Dagestan Caucasus is threatened by the increasingly widespread use of commercial breeds, which in turn risks narrowing the genetic base necessary to increase and maintain existing genetic diversity. For this reason, our research aimed to study the polymorphism of the PRL, PIT‐1, GH genes in red steppe and Caucasian brown cattle raised in the conditions of Dagestan.Methods. Genotyping of red steppe and Caucasian brown cattle was carried out using PCR‐RFLP methods. Using these methods, genetic analysis was carried out and polymorphism of the prolactin, somatotropin and pituitary‐specific transcription factor genes was studied.Results. As a result of the genotyping of an experimental group of red steppe cattle, it was found that the distribution of two alleles and three genotypes (PIT‐1A and PIT‐1B; PIT‐1AA, PIT‐1BB, PIT‐1AB) of the PIT‐1 gene has a specific character. The specificity of the allelic spectrum of the PRL gene is expressed in the high (0.84) frequency of occurrence of the PRLA allele and low (0.16) frequency of the PRLB allele. This is reflected in the presence of homo‐ and heterozygous genotypes with a frequency of occurrence of 73.0; 23.0; 4.0 %, respectively.Conclusion. Applied genetic approaches to improve the productive and breed qualities of livestock, which are modern and based on a more complete analysis of the genetic diversity and genotype of the studied populations, contribute to the conservation of zoned breeds. At the same time, intrapopulation variability and good adaptability should ensure the sustainable development of dairy cattle breeding in various climatic zones.

Nano-Oregano Essential Oil Improves Rainbow Trout’s (Oncorhynchus mykiss) Growth Performance, Oxidative Status, Fatty Acid Profile of Fillet, Affects Gene Expression and Supports Skin and Intestinal Histomorphometry

Abstract The present study was conducted to investigate the effects of a microencapsulated oregano feed additive containing oregano essential oil named “VISNAT 1” on growth performance, intestinal and skin histomorphometry, serum biochemical parameters, fillet oxidative status and fatty acids (FA) profile of rainbow trout (Oncorhynchus mykiss) under conventional farming conditions. Also, changes in the expression levels of both insulin-like growth factor-1 (IGF-1) and growth hormone 1 (GH-1) genes were assessed. A total of 200 sub-adult trouts (52 g±3.2) were randomly allocated into two different treatments with four replicates each. The control group was fed a basal diet, while oregano group was fed diet supplemented with oregano essential oil at the level of 1.0 kg/t of feed. The results indicate that the phytobiotic product beneficially altered feed, fillet and serum oxidative status and improved performance of trouts. Also, oregano essential oil beneficially affected the histopathology and histomorphometry of intestine and skin. Moreover, oregano oil addition in the rainbow trout diet can initiate mitogenic and anti-apoptotic responses in the liver, which is one of the main actions of IGF-1 receptor promoting body growth and health. As a result, oregano essential oil can be used as a supplement on trouts diet but further investigation upon its action should take place.

Early Investigations of 20-kDa Human Placental GH Show Promise.

Early Investigations of 20-kDa Human Placental GH Show Promise.

Development and characterisation of a novel inhibitory anti-GH monoclonal antibody.

Excess growth hormone (GH) has been implicated in multiple cancer types and there is increasing interest in the development of therapeutic inhibitors targeting GH-GH receptor (GHR) signalling. Here we describe a panel of anti-GH monoclonal antibodies (mAbs) generated using a hybridoma approach and identify two novel inhibitory mAbs (1-8-2 and 1-46-3) that neutralised GH signalling. mAbs 1-8-2 and 1-46-3 exhibited strong inhibitory activity against GH-dependent cell growth in a Ba/F3-GHR cell viability assay, with EC50 values of 1.00 ± 0.27 and 0.5 ± 0.1 µg/mL, respectively. Cross-reactivity with the human placental hormones, placental lactogen (PL) and placental GH, was observed by ELISA, but neither antibody cross-reacted with mouse GH or human prolactin (PRL). mAb 1-8-2 had a binding affinity for GH of KD 0.62 ± 0.5 nM, while mAb 1-46-3 had a KD of 2.68 ± 0.53 nM, as determined by bio-layer interferometry. mAb 1-46-3 inhibited GH-dependent signal transduction in T-47D and LNCaP cancer cell lines and reduced GH-dependent cell growth and migration in the breast cancer cell line T-47D. mAb 1-46-3 inhibited T-47D cell viability more effectively than the GHR antagonist B2036. In conclusion, we describe two novel inhibitory anti-GH mAbs and provide in vitro evidence supporting development of these entities as anti-cancer therapeutics.

THU385 Refractory Hyperglycemia As Main Presenting Symptom In A Patient With Acromegaly

Abstract Disclosure: T. Rave: None. J. Vidovic: None. Y. Gu: None. Acromegaly is a rare disorder caused by the overproduction of growth hormone (GH) from an anterior pituitary adenoma. GH regulates glucose control and about 10% of patients with acromegaly can have complications of hyperglycemia. GH stimulates hepatic release of insulin-like growth hormone-1 (IGF-1), which increases gluconeogenesis and lipolysis and decreases glucose uptake throughout the body. The increase in gluconeogenesis and decrease in glucose uptake results in hyperglycemia. The excess release of fatty acids increases insulin resistance. In this case report we present a case of hyperglycemia resistant to multiple modes of medical management with limited acromegaly features found to have acromegaly induced hyperglycemia. A 58-year-old male with a past medical history of type II diabetes mellitus, hypertension, and obesity presented to the endocrinology clinic with treatment resistant hyperglycemia. The patient also endorsed having progressive carpal tunnel symptoms. He had been using an insulin pump and requiring 3 or more boluses per day for the last 6 months. Trulicity was added in addition to current insulin pump therapy, however, sugars remained elevated with an unimproved A1c level of 9% and a fructosamine level of 538 µmol/L correlating to an A1c of 10.8%. An IGF-1 level was sent to rule out acromegaly in the setting of carpal tunnel symptoms. The IGF-1 resulted in 580 ng/mL with a z-score of +5.1. The patient underwent a GH suppression test with a glucose load which showed a significantly elevated nadir GH level of 26.3 ng/mL. Of note, the patient did not have other acromegaly symptoms such as frontal bossing, ring or shoe enlargement, coarse facial features, headaches or vision changes. An MRI pituitary was obtained which was notable for an enlarged pituitary gland with heterogeneous signal, measuring approximately 2.0cm CC x 1.5cm AP x 1.7cm TV, with the pituitary stalk deviated to the left. At this time the intervention for hyperglycemic therapy shifted. The patient was started on octreotide and referred to neurosurgery for transsphenoidal surgery. The pathophysiology of type II diabetes is complex and multifaceted. Additionally, secondary causes of hyperglycemia must be considered in refractory cases, such as in this patient. This case highlights the importance of considering acromegaly and other hormonal conditions in the treatment of patients with uncontrolled hyperglycemia, even in otherwise asymptomatic patients. Presentation: Thursday, June 15, 2023