Hormone Insulin-like Growth Factor Research Articles

Evaluation of gray-matter and white-matter microstructural abnormalities in children with growth hormone deficiency: a comprehensive assessment with synthetic magnetic resonance imaging.

Pediatric growth hormone deficiency (GHD) is a disease resulting from the impaired growth hormone-insulin-like growth factor-1 (GH-IGF-1) axis, but the effects of GHD on children's behavior and brain microstructural structure alterations have not yet been fully clarified. We aimed to investigate the quantitative profiles of gray matter and white matter in pediatric GHD using synthetic magnetic resonance imaging (MRI). The data of 50 children with GHD and 50 typically developing (TD) children were prospectively collected. Group differences in brain volumetric parameters, individual-level T1 and T2 relaxometry values, and myelin volume fraction (MVF) were assessed. Subsequently, magnetic resonance-based indices with significant differences between groups were correlated with clinical variables via partial correlation. Compared with TD children, children with GHD showed significantly decreased whole-brain gray-matter volume [P false discovery rate (PFDR) <0.001] and increased non-gray-matter/white-matter/cerebrospinal fluid (NoN) volume (PFDR<0.001). For gray-matter microstructural profiles, altered T1 and T2 relaxometry values in children with GHD were mainly distributed in the default mode (PFDR<0.001) and central executive networks (PFDR<0.001). For white-matter microstructural profiles, widespread increased regional MVF was mainly distributed in the corpus callosum, corticospinal tract, internal capsule, external capsule, and cingulum (all PFDR values <0.001). Meanwhile, the T2 relaxation values in the left cuneus (r=0.400; P=0.005) and MVF in the right corticospinal tract (r=0.313; P=0.032) had a positive relationship with IGF-1. Altered T1 and T2 relaxometry values and MVF in gray and white matter indicate the relevance of the default mode, central executive, somatosensory, visual, and cerebellar networks underlying pediatric GHD, which may imply the involvement of the GH-IGF-1 axis and myelin in the pathophysiological mechanism of GHD. Moreover, the brain microstructure alteration in cortico-striatal-limbic loop might be influenced by the GH-IGF-1 axis and play an important role in the behavioral impairments in children with GHD.

Lysosomal enzyme binding to the cation-independent mannose 6-phosphate receptor is regulated allosterically by insulin-like growth factor 2.

The cation-independent mannose 6-phosphate receptor (CI-MPR) is clinically significant in the treatment of patients with lysosomal storage diseases because it functions in the biogenesis of lysosomes by transporting mannose 6-phosphate (M6P)-containing lysosomal enzymes to endosomal compartments. CI-MPR is multifunctional and modulates embryonic growth and fetal size by downregulating circulating levels of the peptide hormone insulin-like growth factor 2 (IGF2). The extracellular region of CI-MPR comprises 15 homologous domains with binding sites for M6P-containing ligands located in domains 3, 5, 9, and 15, whereas IGF2 interacts with residues in domain 11. How a particular ligand affects the receptor's conformation or its ability to bind other ligands remains poorly understood. To address these questions, we purified a soluble form of the receptor from newborn calf serum, carried out glycoproteomics to define the N-glycans at its 19 potential glycosylation sites, probed its ability to bind lysosomal enzymes in the presence and absence of IGF2 using surface plasmon resonance, and assessed its conformation in the presence and absence of IGF2 by negative-staining electron microscopy and hydroxyl radical protein footprinting studies. Together, our findings support the hypothesis that IGF2 acts as an allosteric inhibitor of lysosomal enzyme binding by inducing global conformational changes of CI-MPR.

12525 Feline Hypersomatotropism In The USA And Canada: Demographics Of 4620 Cats With Presumed Acromegaly

Abstract Disclosure: R.J. Egbert: None. R.C. Fowkes: None. S.J. Niessen: None. B.K. Petroff: None. Spontaneous models of endocrinopathies are powerful tools to understand disease etiology. Endocrine diseases in companion animals are particularly useful to study, as they share their environment with humans and typically present with clinical disease that phenocopies human symptoms. One such disease in domestic cats, hypersomatotropism (HST, feline acromegaly), is a disorder of excessive growth hormone and increased IGF-1 (Insulin like Growth Factor 1), usually caused by hyperplasia or neuroendocrine tumors of the pars distalis of the pituitary gland. This retrospective study used serum IGF-1 results to investigate population characteristics for domestic cats with HST in the United States and Canada. Laboratory records from 1Jan06 to 31Dec22 were reviewed and animals with a circulating IGF-1 hormone concentration of 190 nmol/L (1,450 ng/mL) or greater were presumed to have acromegaly. This review identified 4,620 such cats with a mean age (n=4,351) of 11.2 years (median: 11.2, range: .5-20.3yr) and mean weight (n=2,086) of 6.03 Kg (median: 5.91, range: 2.27-15.0 Kg). Males outnumbered females in the database, which included 3,048 males and 1,181 females. Domestic Short/Medium/Longhair cats were the most prevalent breed (n=3,563; 77%), followed by Maine Coon cats (n=120; 2.6%) and Siamese cats (n=111, 2.4%). Just under half of the animals (n=2,037, 44%) had a history of diabetes mellitus on the submission form. Most submissions were from the US (n=4,347, 94%) with the most hypersomatotropic cats from California (n=841, 18.2%), New York (n=604, 13.1%), Massachusetts (n=402, 8.7%), Colorado (225, 4.9%), and Texas (200, 4.3%). The mean serum IGF-1 concentration of these animals was 358 nmol/mL (median: 345, range 190-761 nmol/mL). For comparison, an age and sex matched control group of 95 animals with residual samples previously submitted for unrelated testing was selected. The mean IGF-1 concentration for the control group was 97 nmol/mL (median: 85, range 0-311 nmol/mL). In summary, HST is diagnosed most frequently in older male cats in urbanized North America, and potentially displays some breed disposition, suggesting both a genetic and environmental component to the disease etiology. Presentation: 6/2/2024

The analysis of growth performance and expression of growth-related genes in natural gynogenic blunt snout bream muscle derived from the blunt snout bream (Megalobrama amblycephala, ♀) × Chinese perch (Siniperca chuatsi, ♂)

Gynogenesis is an advanced breeding technique that can quickly establish pure lines, increase progenies genetic variation, cultivate strains with higher dominant traits. As a good model for cross order species hybridization, there are few reports on the study of natural gynogenetic blunt snout bream (GBSB), even on the differences in growth between gynogenesis progenies and their parent fish (blunt snout bream♀ and Chinese perch♂). In this research we compared the growth characteristics of the natural GBSB with its parents. It was found that GBSB had a faster growth rate and higher meat content than its female parent, and the diameter and density of muscle fibers were between those of paternal and maternal fish. We performed transcriptome sequencing of muscle tissues from GBSB and BSB, it identified 1353 significant DEGS in the muscle of the GBSB compared to the BSB, with 820 up- and 533 down-regulated genes. And the relative expression of myosins was notable rise in GBSB. In addition, the MRFs of gene structure, motifs, and phylogenetic relations were characterized in BSB and CP. It showed that MRFs and mstn central domain was highly conserved, but the number of conservative motifs in MRFs of CP is generally higher than that of BSB. Further, the relative expression of myosin complex, myogenic regulatory factors (MRFs), growth hormone/insulin-like growth factor (GH/IGF)-axis and most hypothalamic-pituitary-gonadal (HPG)-axis genes in GBSB were higher than that of the female fish and some were closer to that of the paternal fish. Through the distant hybridization between BSB and CP, a gynogenetic progeny with enhanced growth rate compared to the maternal fish was successfully generated. The research has contributed significant insights into the genes and molecular properties associated with muscle development, as well as their potential functional correlations in response to different functional requirements during the growth process of hybrid progeny formed by cross breeding.

Insulin-like growth factor-1 promotes the testicular sperm production by improving germ cell survival and proliferation in high-fat diet-treated male mice.

A decrease in semen volume among men is comparable to the rising prevalence of obesity worldwide. The anabolic hormone insulin-like growth factor-1 (IGF-1) can promote proliferation and differentiation in cultured mouse spermatogonial stem cells and alleviate abnormal in vitro spermatogenesis. Additionally, serum IGF-1 level is negatively correlated with body mass index. Whereas the role of IGF-1 in the sperm production in obese men remains unclear. To investigate the therapeutic effect and potential mechanism of IGF-1 on spermatogenesis of high-fat diet (HFD)-induced obesity mice. An HFD-induced obesity mouse model was established. Alterations in testicular morphology, sperm count, proliferation, and apoptosis were observed by H&E staining,immunohistochemistry, immunofluorescence, and Western blotting. Exogenous recombinant IGF-1 was administered to obese mice to investigate the correlations between altered testicular IGF-1 levels and sperm production. The sperm count was reduced, the testicular structure was disordered, and sex hormone levels were abnormal in HFD-fed mice compared with normal diet-fed mice. The expression of proliferation-related antigens such as proliferating cell nuclear antigen (PCNA) and Ki-67 was decreased, while that of proapoptotic proteins such as c-caspase3 was increased in testes from HFD-fed mice. Most importantly, the phosphorylation of insulin-like growth factor-1 receptor (IGF-1R) in testes was decreased due to reductions in IGF-1 from hepatocytes and Sertoli cells. Recombinant IGF-1 alleviated these functional impairments by promoting IGF-1R, Akt, and Erk1/2 phosphorylation in the testes. Insufficient IGF-1/IGF-1R signaling is intimately linked to damaged sperm production in obese male mice. Exogenous IGF-1 can improve survival and proliferation as well as sperm production. This study provides a novel theoretical basis and a target for the treatment of obese men with oligozoospermia.

Changes of GH-IGFs and its relationship with growth retardation in children with bronchial asthma

ObjectiveTo explore the relationship between Growth Hormone Insulin-like Growth Factors (GH-IGFs) and growth retardation in children with bronchial asthma. Methods112 children with bronchial asthma and 50 healthy children were studied. Serum GH, IGF-1, and Insulin-like Growth Factor Binding Protein 3 (IGFBP3) were assessed by ELISA. GH-IGFs-related parameters were compared, and the correlation between the parameters and bronchial asthma severity was analyzed. The bronchial asthma group was divided into the growth retardation group and non-growth retardation group to analyze the diagnostic value of GH-IGFs in growth retardation and the relationship between GH-IGFs and growth retardation. ResultsGH, IGF-1, and IGFBP3 in the bronchial asthma group were lower. GH, IGF-1, and IGFBP3 levels were decreased with the severity of bronchial asthma. GH, IGF-1, and IGFBP3 in the growth retardation group were lower than those in the non-growth retardation group. The AUC of GH-IGFs combined detection was higher than that of GH and IGFBP3 alone detection. GH < 9.27 μg/L and IGF-1 < 179.53 mmoL/L were risk factors for growth retardation in patients with bronchial asthma. ConclusionGH-IGFs-related parameters have diagnostic value for growth retardation in children, and decreased levels of GH and IGF-1 are risk factors for growth retardation in children.

The effect of suggested exercises according to the ballistic training method on insulin-like growth factor-1 hormone, speed-specific strength of leg muscles, and achievement of the triple jump in advanced athletes

The effect of suggested exercises according to the ballistic training method on insulin-like growth factor-1 hormone, speed-specific strength of leg muscles, and achievement of the triple jump in advanced athletes

Genetic analysis of the PAPP-A2 gene and evaluation of free IGF-1, IGFBP-5, and ALS concentrations in a group of 22 patients with idiopathic short stature.

Short stature is one of the main reasons for consultation in outpatient clinics and paediatric endocrinology departments and is defined as height below the 3rd centile or less than -2 standard deviations (SDs). The study's overarching aim was to analyse the PAPP-A2 gene at mutation sites described to date and at exons 3, 4, and 5, which encode the fragment of the catalytic domain with the active site of the pregnancy-associated plasma protein A2 (PAPP-A2) protein. The secondary aims of the study were clinical and auxological analysis of a group of patients with idiopathic short stature and biochemical analysis of growth hormone-insulin-like growth factor-1 (GH-IGF-1) axis parameters not assessed as part of the routine diagnosis of short stature, such as free IGF-1, insulin-like growth factor binding protein 5 (IGFBP-5), and acid-labile subunit (ALS) levels. Molecular analysis of the PAPP-A2 gene was performed using polymerase chain reaction (PCR) and direct sequencing. Biochemical analysis of free IGF-1, IGFBP-5, and ALS was performed by enzyme-linked immunosorbent assay (ELISA). The mean height standard deviation score (HSDS) in the study group was -2.95. None of the patients exhibited previously described mutations in the PAPP-A2 gene or mutations in exons 3, 4, and 5 encoding the fragment of catalytic domain with the active site of the PAPP-A2 protein. In 4 patients, the known, non-pathogenic, heterozygotic polymorphism c.2328C>T(rs10913241) in exon 5 was found. Free IGF-1 levels correlate better with height and HSDS than total IGF-1 levels. The previously described mutations in the PAPP-A2 gene and mutations in exons 3, 4, and 5 encoding the fragment of catalytic domain with the active site of the PAPP-A2 protein were not detected; only the known and non-pathogenic, heterozygotic polymorphism c.2328C>T(rs10913241) in exon 5 of the PAPP-A2 gene was observed.

Diagnostic significance and considerations of growth hormone stimulation testing and insulin-like growth factor 1 in growth hormone deficiency

The growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis is an essential component of the hypothalamic-pituitary growth hormone axis and plays a crucial role in childhood growth and development. Disruptions and abnormalities in the GH/IGF-1 signaling pathway and its pathways typically manifest as short stature in children. Children with short stature often undergo GH stimulation testing and IGF-1 level measurements to differentiate growth hormone deficiency (GHD) from other causes of growth delay. This article aims to analyze and elucidate the values of GH stimulation testing and IGF-1 measurement, providing reference for the diagnosis of GHD in children.

Environmentally relevant concentrations of Mn2+ disrupts the endocrine regulation of growth in juvenile Yunlong groupers (Epinephelus moara♀×Epinephelus lanceolatus♂)

Even though manganese is a bioelement essential for metabolism, excessive manganese levels in water can be detrimental to fish development and growth. Therefore, the aim of this study was to evaluate the effects of Mn2+ (0, 0.5,1, 2, and 4 mg·L−1) exposure for 30 d on the growth performance, growth hormone/insulin-like growth factor (GH/IGF) axis, hypothalamic-pituitary-thyroid (HPT) axis, and monoaminergic neurotransmitters of Epinephelus moara♀×Epinephelus lanceolatus♂(Yunlong grouper). Compared with the control and low Mn2+concentration groups of (0.5 and 1 mg·L−1), the high concentration of Mn2+ (4 mg·L−1) significantly reduced body weight (BW), body length (BL), weight gain rate (WGR), and specific growth rate (SGR), increased the feed coefficient rate (FCR) and mortality of Yunlong groupers (P < 0.05). Further, the levels of GH and IGF, along with the expression of ghra and ghrb were significantly reduced after exposure to 2 and 4 mg·L−1 Mn2+for 30 d, whereas the expression of sst5 was significantly up-regulated after exposure to 2 and 4 mg·L−1 Mn2+for 20 and 30 days. Moreover, Mn2+exposure increased thyroid hormone (T3) and thyroid stimulating hormone (TSH) contents, accompanied by increased mRNA levels of dio1 and dio2, however, the T4 level was decreased. Finally, dopamine (DA) and serotonin (5-HT) levels significantly decreased after long-term exposure to higher concentrations of Mn2+, and the levels their metabolites changed as well, suggesting that the synthesis and metabolism of DA and 5-HT were affected. Accordingly, changes in the GH/IGF and HPT axes-related parameters may be the cause of growth inhibition in juvenile groupers under Mn2+ exposure, indicating that the relationship between endocrine disorder and growth inhibition should not be ignored.

Efficient breeding and growth advantage of all-male population in Lanzhou catfish (Silurus lanzhouensis)

Sex is one of the most valuable traits for aquaculture fish with distinct sexual dimorphisms, and breeding of monosexual populations improves aquaculture efficiency. Lanzhou catfish (Silurus lanzhouensis) with XX/XY sex determination system is an endemic fish in the Yellow River of China and exhibits sexual growth dimorphism. Here, we tracked the body weight, length and width of Lanzhou catfish and found out that males displayed faster growth performance than females from 3 months post fertilization, accompanied by sexually dimorphic expression of growth hormone/insulin-like growth factor (GH/IGF) axis genes. Subsequently, we performed genetic analyses in the self-fertilized family obtained from a hermaphrodite individual. Similar to the artificial gynogenetic family, the offspring of the self-fertilized family had significant higher genetic homozygosity and similarity than that of the sexually reproduced family. More importantly, we used the YY male obtained by self-fertilization to mate with two XX female individuals and reproduced an all-male population with XY sex chromosomes, saving one generation time (3 years) and avoiding estradiol treatment compared with the conventional way of all-male population production. And the all-male population showed an obvious growth advantage over the normal population with both sexes, facilitating the development of catfish aquaculture.

Clinical and genetic evaluation of children with short stature of unknown origin

BackgroundShort stature is a common human trait. More severe and/or associated short stature is usually part of the presentation of a syndrome and may be a monogenic disease. The present study aimed to identify the genetic etiology of children with short stature of unknown origin.MethodsA total of 232 children with short stature of unknown origin from March 2013 to May 2020 were enrolled in this study. Whole exome sequencing (WES) was performed for the enrolled patients to determine the underlying genetic etiology.ResultsWe identified pathogenic or likely pathogenic genetic variants in 18 (7.8%) patients. All of these variants were located in genes known to be associated with growth disorders. Five of the genes are associated with paracrine signaling or cartilage extracellular matrix in the growth plate, including NPR2 (N = 1), ACAN (N = 1), CASR (N = 1), COMP (N = 1) and FBN1 (N = 1). Two of the genes are involved in the RAS/MAPK pathway, namely, PTPN11 (N = 6) and NF1 (N = 1). Two genes are associated with the abnormal growth hormone-insulin-like growth factor 1 (GH-IGF1) axis, including GH1 (N = 1) and IGF1R (N = 1). Two mutations are located in PROKR2, which is associated with gonadotropin-releasing hormone deficiency. Mutations were found in the remaining two patients in genes with miscellaneous mechanisms: ANKRD11 (N = 1) and ARID1A (N = 1).ConclusionsThe present study identified pathogenic or likely pathogenic genetic variants in eighteen of the 232 patients (7.8%) with short stature of unknown origin. Our findings suggest that in the absence of prominent malformation, genetic defects in hormones, paracrine factors, and matrix molecules may be the causal factors for this group of patients. Early genetic testing is necessary for accurate diagnosis and precision treatment.

The regulation of human organic anion transporter 4 by insulin-like growth factor 1 and protein kinase B signaling

Human organic anion transporter 4 (hOAT4), mainly expressed in the kidney and placenta, is essential for the disposition of numerous drugs, toxins, and endogenous substances. Insulin-like growth factor 1 (IGF-1) is a hormone generated in the liver and plays important roles in systemic growth, development, and metabolism. In the current study, we explored the regulatory effects of IGF-1 and downstream signaling on the transport activity, protein expression, and SUMOylation of hOAT4. We showed that IGF-1 significantly increased the transport activity, expression, and maximal transport velocity Vmax of hOAT4 in kidney-derived cells. This stimulatory effect of IGF-1 on hOAT4 activity was also confirmed in cells derived from the human placenta. The increased activity and expression were correlated well with the reduced degradation rate of hOAT4 at the cell surface. Furthermore, IGF-1 significantly increased hOAT4 SUMOylation, and protein kinase B (PKB)-specific inhibitors blocked the IGF-1-induced regulations on hOAT4. In conclusion, our study demonstrates that the hepatic hormone IGF-1 regulates hOAT4 expressed in the kidney and placenta through the PKB signaling pathway. Our results support the remote sensing and signaling theory, where OATs play a central role in the remote communications among distal tissues.

Label-free electrochemical immunosensor for detection of insulin-like growth factor-1 (IGF-1) using a specific monoclonal receptor on electrospun Zein-based nanofibers/rGO-modified electrode

A novel electrochemical immunosensor was developed for ultrasensitive determination of the hormone insulin-like growth factor 1 (IGF-1) based on immobilization of a specific monoclonal antibody on the electrospun nanofibers of Polyacrylonitrile (PAN)/Zein-reduced graphene oxide (rGO) nanoparticle. The nanofibers deposited on glassy carbon electrode (GCE) showed good electrochemical behaviors with synergistic effects between PAN, Zein, and rGO. PAN/Zein nanofibers were used due to flexibility, high porosity, good mechanical strength, high specific surface area, and flexible structures, while rGO nanoparticles were used to improve the detection sensitivity and anti-IGF-1 immobilizing. Different characterization techniques were applied consisting of FE-SEM, FT-IR, and EDS for the investigation of morphological features and nanofiber size. The redox reactions of [Fe(CN)6]4−/3− on the modified electrode surface were probed for studying the immobilization and determination processes, using differential pulse voltammetry (DPV) and cyclic voltammetry (CV). Under optimal conditions, LOD (limit of detection) and LOQ (limit of quantification) were obtained as 55.72 fg/mL and 185.73 fg/mL respectively, and sensitivity was acquired 136.29 μA/cm2.dec. Moreover, a wide linear range was obtained ranging from 1 pg/mL to 10 ng/mL for IGF-1. Furthermore, the proposed method was applied for the analysis of IGF-1 in several human plasma samples with acceptable results, and it also exhibited high selectivity, stability, and reproducibility.

Microcystin-LR immersion caused sequential endocrine disruption and growth inhibition in zebrafish (Danio rerio) from fertilization to sexual differentiation completion

Microcystin-LR (MC-LR) is a highly toxic congener and is also one of the most commonly found. Recent studies have demonstrated that MC-LR can disrupt growth and endocrine in fish, but how it works at the stage of the sex differentiation period had not been determined to date. In this study, zebrafish (Danio rerio) embryos were exposed to MC-LR (0 and 10 μg/L), and sampled at 14, 28, and 42 days post fertilization (dpf), respectively. The results demonstrated that MC-LR caused the growth inhibition of zebrafish at 42 dpf. The expression levels of genes related to the growth hormone/insulin-like growth factor (GH/IGF) and hypothalamic-pituitary-thyroid (HPT) axes, as well as the levels of hormone 3,5,3′- triiodothyronine (T3) and thyroxine (T4), were significantly decreased at all time points. A significant decrease in the ratio of testosterone and estradiol (T/E2) were detected at 28 and 42 dpf in MC-LR group along with changes in genes related to the hypothalamic-pituitary–gonadal (HPG) axis. The result of sex ratio showed that the percentage of females was up to 61.84%, indicating a estrogenic effect induced by MC-LR. The significant changes on hormone levels and gene transcripts occurred mainly in the stage of sex differentiation. The correlation analysis further suggested that key cross-talks among three endocrine axes may be the growth hormone releasing hormone (GHRH), transthyretin (TTR) and gonadotropin releasing hormone (GnRH) signaling molecules. Overall, our findings provide a new insight for understanding the mechanisms by which MC-LR affects fish growth and reproduction during gonadal development.

Dietary choline can partially spare methionine to improve the feeds utilization and immune response in juvenile largemouth bass (Micropterus salmoides): Based on phenotypic response to gene expression

Present study was conducted to explore the interrelationship between dietary methionine and choline in feed formulations for largemouth bass (Micropterus salmoides). Four isonitrogenous (51.0%) and isolipidic (14.0%) diets were formulated supplemented or not supplemented with methionine and choline: NC diet (basic diet), Met diet (basic diet supplemented with methionine), Cho diet (basic diet supplemented with choline) and PC diet (basic diet supplemented with methionine and choline). Fish with an initial body weight of 8.01 ± 0.08 g were fed with each diet for 8 weeks. Significant interactions were found between dietary methionine and choline on growth performance, plasma nutrient concentration, genes expression level of nutrient sensing signaling pathways, nutrient metabolism and immune response. Dietary methionine addition had great effects on improving weight gain rate (WGR), specific growth rate (SGR) and Feed efficiency ratio (FER), while choline supplementation only increased FER (P＜0.05). Both added methionine and choline had higher WGR, SGR and FER than the other groups (P＜0.05). Moreover, compared with NC group, PC, Met and Cho groups also activated growth hormone/insulin-like growth factor (GH-IGF), mammalian target of rapamycin (mTOR) pathway and shut down amino acid response (AAR) pathway to further enhanced glucose, lipid synthesis (P＜0.05). Dietary choline and methionine were similar in regulating the activity of signaling pathways (P > 0.05). Supplemented both together had the most significant effect on promoting nutrient accumulation and improving feed efficiency (P＜0.05). Furthermore, methionine and choline addition also enhanced the gene expression level of key regulators in immune response. Combined supplementation could improve this effect than the individual supplementation to a certain degree. Therefore, when methionine met the requirement of largemouth bass, choline supplementation could further raise the utilization of methionine and partially spare methionine efficiently. This study provided a more reasonably method for using choline to improve growth and feed utilization which could maximize growth and avoid the toxic effect of excessive methionine addition in diets.

Inflammation induces stunting by lowering bone mass via GH/IGF-1 inhibition in very preterm infants.

Sustained systemic inflammatory response (SIR) was associated with poor postnatal growth in very preterm infants (VPI). We hypothesize that VPI with sustained SIR will exhibit linear growth retardation related to lower bone mass accrual mediated by GH/IGF-1 axis inhibition at term corrected age (CA). C-reactive protein (CRP), procalcitonin (PCT), growth hormone (GH), insulin-like growth factor 1 (IGF-1), calcium, phosphorus, alkaline phosphatase, anthropometric, nutritional, neonatal and maternal data were collected prospectively in 23 infants <32 weeks gestational age. Body composition using dual-energy X-ray absorptiometry was performed at term CA. Analysis was undertaken with multiple linear regression models. At term CA 11 infants with sustained SIR compared with 12 infants without sustained SIR present significantly lower IGF-1, length z-score (LZS), bone mineral content (BMC) and lean mass (LM), and higher GH and fat mass (FM). LZS was associated significantly with PCT, BMC with IGF-1, FM and LM with CRP, GH with bronchopulmonary dysplasia and CRP, and IGF-1 with invasive mechanical ventilation, CRP and PCT. In addition to the known effect on linear growth failure, sustained SIR induces lower bone mass accrual related to higher GH and lower IGF-1 levels in VPI. Very preterm infants (VPI) with sustained systemic inflammatory response (SIR) compared with VPI without SIR present stunting, lower bone mass, higher GH and lower IGF-1 levels at term corrected age. SIR may help to explain the influence of non-nutritional factors on growth and body composition in VPI. SIR induces postnatal stunting related to lower bone mass accrual via GH/IGF-1 axis inhibition in VPI. VPI with SIR need special attention to minimize inflammatory stress, which could result in improved postnatal growth. Research on inflammatory-endocrine interactions involved in the pathophysiology of postnatal stunting is needed as a basis for new interventional approaches.

Insulin-like growth factor-1 on cycle day 2 and assisted reproductive techniques outcome: A cross-sectional study.

Individualized assisted reproductive techniques (ART) can improve ART outcomes. Some studies suggested using insulin-like growth factor-1 (IGF-1) level on cycle day 2 for individualized ART. To investigate the relationship between serum levels of IGF-1 on day 2 of the cycle and ART outcomes. In this cross-sectional study, cycle day 2 serum levels of IGF-1 were measured in 175 women aged between 18-44 yr as candidates for in vitro fertilization or intracytoplasmic sperm injection. All participants received antagonist protocol, and the relationship between serum levels of IGF-1 and ART outcomes according to the number of oocytes were investigated; poor responders (oocytes 5), normal responders (oocytes 5-15), and hyper responders (oocytes 15). Poor responders had higher serum level of IGF-1 when compared with normal and hyper-responders; however,this difference was not statistically significant (p = 0.41). The serum levels of IGF-1 in women with zero retrieved oocytes and those cycles that were canceled for the inappropriate ovarian response were not significantly different compared to other women in the group of poor responders. An inverse relationship was observed between the serum level of IGF-1 and anti-Mullerian hormone. Furthermore, no significant relationship between serum level of IGF-1 with age, body mass index, number of 2 pronucleus, and number of embryos was observed. According to our results, the serum levels of IGF-1 may not be able to predict ART outcomes. It seems necessary to conduct more studies with larger sample size.

Abstract WP218: Intraperitoneal Igf1 Treatment Ameliorates The Chronic Impact Of Ischemic Stroke In Reproductively Senescent Female Rats And Repairs The Gut While Icv-igf-1 Does Not

Background: Our previous studies have shown that reproductively senescent (RS) female rats, who have lower circulating levels of the peptide hormone Insulin-like Growth Factor (IGF-1), display worse outcomes after a stroke event than young adult female rats. ICV administration of IGF-1, decreases infarct volume, improves sensory motor performance, and reduces cytokine levels in the ischemic hemisphere of RS females as compared to vehicle-treated controls. Yet, icv IGF1 administration failed to attenuate peripheral inflammation and depressive behaviors in the chronic phase of stroke. In view of the evidence that stroke induces gut dysbiosis, and that gut dysfunction is implicated in depressive and cognitive behaviors, we hypothesize that, unlike icv administration of IGF-1, which is restricted to the brain, systemic i.p. administration of IGF1 would repair the gut, attenuate peripheral cytokine levels and improve long-term behavior outcomes. Methods: Acyclic middle-aged Sprague Dawley female rats (9-11 mos) were subjected to endothelin-1 induced middle cerebral artery occlusion (MCAo) or sham operation. Animals received IGF1 via i.p. injections 4h post MCAo and 24 h post MCAo, or icv infusions, while controls received vehicle. Sensory motor tests, blood and gut samples were acquired pre and post MCAo. Animals were terminated either in the acute phase (2d) or chronic phase (30d). The latter group was also subject to tests of cognition and depressive-like behavior. Results: In contrast to icv treatment, i.p.-IGF-1 did not reduce infarct volume or acute sensory motor impairment, but significantly attenuated circulating levels of several inflammation associated cytokines. In addition, ip-IGF-1 significantly attenuated post stroke gut dysmorphology, by preserving villus:crypt ratio and the mucin barrier. Furthermore, in the chronic phase, i.p.-IGF1 attenuated cognitive decline post stroke in the NORT and Barnes Maze tasks, while icv IGF-1 did not. Conclusion: Since long term disability after stroke is correlated with elevated levels of peripheral cytokines, our data suggest that systemic IGF1 may be a better therapeutic option for long term outcomes.Supported by NS074895 to FS. YEH is supported by a generous gift from the WoodNext Foundation.

Cysteamine-supplemented diet for cashmere goats: A potential strategy to inhibit rumen biohydrogenation and enhance plasma antioxidant capacity

Cysteamine (CS), as a feed supplement, can increase the level of growth hormone (GH) in the blood, promote animal growth. However, little attention has been paid to the effects of CS on the rumen microbiome and metabolic profile in cashmere goats. This study aimed to assess the effects of rumen microbiota, metabolites, and plasma antioxidative capacity induced by CS supplementation in cashmere goats. We selected 30 Inner Mongolia white cashmere goat ewes (aged 18 months), and randomly separate the goats into three groups (n = 10 per group) to experiment for 40 days. Oral 0 (control group, CON), 60 (low CS, LCS), or 120 mg/kg BW−1 (high CS, HCS) coated CS hydrochloride every day. Using 16S and internal transcribed spacer (ITS) rRNA gene amplicon sequencing, we identified 12 bacterial and 3 fungal genera with significant changes among the groups, respectively. We found a significant increase in rumen NH3-N and total volatile fatty acid (TVFA) concentrations in the LCS and HCS groups compared with the CON. With untargeted LC–MS/MS metabolomics, we screened 59 rumen differential metabolites. Among the screened metabolites, many unsaturated and saturated fatty acids increased and decreased with CS treatment, respectively. CS supplementation increased the levels of plasma total antioxidant capacity (T-AOC), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), GH, and insulin-like growth factor-1(IGF-1). Spearman correlation analysis revealed that the abundance of U29-B03, Lactococcus, and Brochothrix were positively associated with the levels of δ2-THA, TVFA and antioxidant capacity. In conclusion, CS significantly affected rumen microbiota and fermentation parameters, and ultimately inhibited the biohydrogenation of rumen metabolites, enhanced plasma antioxidant capacity, and regulated some hormones of the GH–IGF-1 axis. This study provides an overall view into the CS application as a strategy to improve health production in cashmere goats.