Plasma Growth Hormone Research Articles

The Relationship Between Serum Growth Hormone, Seminal Plasma Growth Hormone, and Sperm Parameters in Patients with Acromegaly in Remission

The Relationship Between Serum Growth Hormone, Seminal Plasma Growth Hormone, and Sperm Parameters in Patients with Acromegaly in Remission

Identification and differentiation of somapacitan, a long-acting growth hormone derivative, and recombinant human growth hormone in equine plasma by LC-HRMS for doping control purpose

Somapacitan, a long-acting growth hormone derivative, and recombinant human growth hormone (rhGH) are protein-based drugs generally used to treat growth disorders and GH deficiency in humans. Due to their potential to enhance the horse performance, the use of these drugs is prohibited at-all-times by the International Federation of Horseracing Authorities for horseracing and the Fédération Equestre Internationale for equestrian sports. In this study, we developed a test method for the identification and differentiation of somapacitan and rhGH in equine plasma by using liquid chromatography high-resolution mass spectrometry (LC–HRMS). The method involved C4 solid-phase extraction after ammonium sulfate precipitation, followed by chloroform/methanol precipitation, trypsin digestion, and analysis by LC-HRMS. The discriminative identification of somapacitan and rhGH was successfully achieved through the detection of their respective unique T10 peptide fragments. Noteworthy, the T10 peptide fragment of somapacitan was detected with its side chain structure remaining intact. The limit of identification (confirmation) (LOI) was determined to be 5 ng/mL for somapacitan and 2 ng/mL for rhGH in equine plasma, while the limit of detection (LOD) was 5 ng/mL for somapacitan and 1 ng/mL for rhGH. Furthermore, using the peptide fragments T1, T8, and T9 (which are shared between somapacitan and rhGH), the presence of somapacitan in equine plasma could be confirmed with higher sensitivity, achieving down to LOIs of 2 ng/mL and LODs of 1 ng/mL. The method was validated with respect to specificity, identification capability, robustness, precision, and reproducibility, paving the way for the analysis of post-administration samples from our already planned administration trials and future potential positive cases.

Impact of an extended light regimen imposed during nursery period on the performance and lipid metabolism of weanling pigs.

This study aimed to assess the impact of a prolonged photoperiod on the growth performance and lipid metabolism of weaned piglets. Twenty-four piglets weaned at 28 days of age were randomly dichotomized into two groups that were alternatively subjected to either long photoperiod (LP) group (16L:8D) or short photoperiod (SP) group (10L:14D) for 42days. Four replicates of three animals per replicates were used per experimental treatment. Our results demonstrated that prolonged photoperiod increased piglet body weight, average daily weight gain (ADG), backfat thickness (BF), backfat index during the nursery period, and increased ADG, average daily feed intake (ADFI), and decreased the F/G of piglets during the experiment days 29 to 42. Meanwhile, we observed LP piglets' plasma melatonin, growth hormone and serotonin levels were decreased at 14 d and 42 d compared to SP piglets. Moreover, up-regulated mRNA or protein expression of PPARγ and CEBPα, and lower mRNA or protein expression of MTR1, ATGL, HSL, PPARα, and CPT1α, were observed in back subcutaneous fat (BSF) of LP group compared with that of SP group. Significant increases were observed in the mRNA or protein contents of lipogenic genes, including C/EBPα, SREBP-1c, ACCα, and FAS, in the liver of LP piglets, whereas CPT1α and ACOX1 mRNA levels and PPARα and MTR1 protein expression were significantly down-regulated in LP group compared to SP group. Extended photoperiod also increased lipid content in longissimus dorsi muscle (LDM) that was associated with higher mRNA or protein levels of SREBP-1c, ACCα, FAS, Pref1, and LPL, decreased mRNA or protein contents of LeptinR, MTR1, HSL, and ACOX1. Together, these findings suggest that there is an advantage, in terms of growth performance and fat deposition, in imposing a prolonged light program (16-h light/day) on nursery piglets to alleviate the negative aspects of weaning stress.

D-Aspartate Stimulates Growth Hormone Secretion in Wethers.

Growth hormone (GH) is an essential factor in enhancing the productivity of animals. In ruminants, L-aspartate (L-Asp) stimulates the secretion of GH; however, the effect of D-Asp on GH remains unknown. Here, we examined the effect of D-Asp on GH secretion in wethers. Blood GH, insulin, adrenaline, noradrenaline, non-esterified fatty acid (NEFA), and glucose concentrations were evaluated in response to the intravenous infusion of a high-dose (0.1 mmol/kg/min) of D-Asp for 20min. Further, concentrations of these biomolecules were evaluated when a low-dose (0.05 mmol/kg/min) of D-Asp was continuously infused intravenously for 20min. Finally, the direct effect of D-Asp on GH secretion was determined using cultured sections of the anterior pituitary tissue from wethers. Infusion of the high-dose of D-Asp markedly increased blood GH concentrations (P < 0.05), resulting in an increase in the area under the curve (AUC). Plasma GH concentrations and AUC also increased in response to infusion of a low D-Asp dose. Infusion of a high and low D-Asp dose caused a prolonged reduction in plasma insulin concentrations, and the AUC was lower (P < 0.05). Plasma NEFA concentrations gradually increased after the end of D-Asp infusion, with a low D-Asp dose infusion resulting in significantly higher concentrations at 90min (P < 0.05). Plasma adrenaline, noradrenaline, and glucose concentrations did not show significant changes despite differences in the dose of D-Asp. Although D-Asp treatments stimulated GH secretion in the cultured sections of pituitary tissues, the effect was not significant. These results suggest that D-Asp stimulates the secretion of GH in wethers through not only a direct action on the pituitary gland but also through another pathway of GH stimulation.

In Vivo Effects of a GHR Synthesis Inhibitor during Prolonged Treatment in Dogs

Background: The activation of the growth hormone receptor (GHR) is a major determinant of body growth. Defective GHR signaling, as seen in human Laron dwarfism, resulted in low plasma IGF-1 concentrations and limited growth, but also marked absence in the development of breast cancer and type 2 diabetes. In vitro, we identified a small molecule (C#1) that inhibits the translation of GHR mRNA to receptor protein. Methods: Before its application in humans as a potential anticancer drug, C#1 was tested in animals to evaluate whether it could be administered to achieve a plasma concentration in vivo that inhibits cell proliferation in vitro without causing unwanted toxicity. To evaluate the efficacy and toxicity of C#1, a group of six intact female Beagle dogs was treated daily each morning for 90 days with an oral solution of C#1 in Soiae oleum emulgatum at a dose of 0.1 mg/kg body weight. During treatment, dogs were closely monitored clinically, and blood samples were taken to measure plasma C#1 concentrations, complete blood counts (CBC), clinical chemistry, and endocrinology. At the end of the treatment, dogs were euthanized for gross and histopathological analysis. An additional group of six female Beagle dogs was included for statistical reasons and only evaluated for efficacy during treatment for 30 days. Results: Daily administration of C#1 resulted in a constant mean plasma concentration of approximately 50 nmol/L. In both groups, two out of six dogs developed decreased appetite and food refusal after 4–5 weeks, and occasionally diarrhea. No significant effects in CBC or routine clinical chemistry were seen. Plasma IGF-1 concentrations, used as biomarkers for defective GHR signaling, significantly decreased by 31% over time. As plasma growth hormone (GH) concentrations decreased by 51% as well, no proof of GHR dysfunction could be established. The measured 43% decrease in plasma acylated/non-acylated ghrelin ratios will also lower plasma GH concentrations by reducing activation of the GH secretagogue receptor (GHSR). C#1 did not directly inhibit the GHSR in vivo, as shown in vitro. There were no significant effects on glucose, lipid, or folate/homocysteine metabolism. Conclusions: It is concluded that with daily dosing of 0.1 mg C#1/kg body weight, the induction of toxic effects prevented further increases in dosage. Due to the concomitant decrease in both IGF-1 and GH, in vivo inhibition of GHR could not be confirmed. Since the concept of specific inhibition of GHR synthesis by small molecules remains a promising strategy, searching for compounds similar to C#1 with lower toxicity should be worthwhile.

8396 Growth Hormone Secretion after Glucagon Stimulation is Increased in Individuals with History of Bariatric Surgery

Abstract Disclosure: L. Pei: None. C. Cummings: None. H. Saeed: None. M. Farahmandsadr: None. A. Amore: None. A. Sheehan: None. R. Ferraz-Bannitz: None. D.C. Simonson: Stock Owner; Self; GI Windows. Other; Self; wife owns Phase V Technologies. M. Patti: Advisory Board Member; Self; data and safety monitoring board on Fractyl Health. Consulting Fee; Self; AstraZeneca, Hamni, MBX Biosciences. Grant Recipient; Self; Receive investigator-initiated research funding from Dexcom. Background: Growth hormone (GH) is an important counterregulatory hormone and regulator of hepatic glucose metabolism. Previous studies demonstrated increased plasma GH and reduced plasma growth hormone receptor (GHR) after bariatric surgery in both rodents and humans. Moreover, plasma GHR was identified as mediator of improved glycemic control after Roux-en-Y gastric bypass (RYGB). We now test the hypothesis that altered GH and/or GHR levels contribute to post-bariatric hypoglycemia (PBH). Methods: Cross-sectional studies were performed at a single academic institution. GH secretion was assessed after 1mg IV glucagon (GCG) and during hyperinsulinemic-hypoglycemic clamp in 3 groups: 1) post-RYGB without hypoglycemia symptoms (RnonH) (20F, age 51±11 (mean±SD) y, BMI 35±8 kg/m2, HbA1c 5.2±0.3%, 10.6±5.3 years post-surgery), 2) PBH (18F/2M, age 54±12y, BMI 30.5±4.6 kg/m2, HbA1c 5.2±0.3%, 9.4±6.0 years post-surgery), 3) weight-similar controls without upper GI surgery (CON) (6F/4M, age 47.1±13.1y, BMI 31.9±5.7 kg/m2, HbA1c 5.4±0.3%). Plasma GHR and GH were measured via ELISA. Results: Fasting GH did not differ between groups (mean±SE, CON: 285±78, RnonH: 860±179, PBH: 980±284 pg/mL, P=0.16). Peak incremental glucose response to GCG, ranging from 46-59 mg/dL, did not differ between groups. At 120 min after GCG, GH was significantly higher in both PBH and RnonH vs. CON (PBH: 3018±678, RnonH: 2521±656, CON: 481±137 pg/mL, ANOVA P= 0.012, PBH vs. CON P=0.003, RnonH vs. CON P=0.02). Peak GH in PBH was significantly higher vs. CON (3431± 655 vs. 547±153 pg/mL, P=0.03), but did not differ in RnonH vs. PBH. Peak GH was inversely correlated with postoperative duration in PBH only (r=-0.49, P=0.03), with BMI in both surgical groups (PBH: r=-0.49, P=0.03, RnonH: r=-0.57, P=0.009) and with percent body fat (impedance plethysmography) in the combined surgical group (r=-0.51, P=0.0007). In contrast, GH during hyperinsulinemic hypoglycemia did not differ between groups (CON: 9660 ±2588, RnonH: 7759±1751, PBH: 7309±1549 pg/mL, P=0.3) at similar degrees of hypoglycemia (CON: 54.8±1.5, RnonH: 50.7±1.0, PBH: 50.9±1.4 mg/dL). Fasting plasma GHR did not differ (CON: 23.3±3.8, RnonH: 19.4±2.8, PBH: 13.8±2.1 ng/mL, P=0.10). GHR was correlated with percent fat mass in the combined surgical group (r=0.56, P=0.0003) but not in CON. Conclusion: Plasma GH did not differ as a function of prior RYGB, with or without hypoglycemia, in the fasting state or in response to insulin-induced hypoglycemia. However, GCG-stimulated GH levels were 5-6-fold higher in individuals with history of RYGB, numerically higher in PBH, and inversely related to body fat and postop duration. Together these results suggest that reduced GH is not likely driving hypoglycemia in PBH, but that alterations in glucagon-mediated GH secretion and/or action may contribute to observed metabolic effects of RYGB. Presentation: 6/1/2024

Identification of candidate genes and pathways involved in the establishment of sexual size dimorphism in the olive flounder (Paralichthys olivaceus) using RNA-seq

Olive flounder (Paralichthys olivaceus) is a valuable mariculture fish that shows female-biased sexual size dimorphism (SSD), yet the molecular mechanisms responsible for this phenomenon remain poorly understood. In this study, the growth differences between females and males were compared, and comparative transcriptome analyses of brains/pituitaries, livers, muscles, and gonads from 13-month-old females and males were performed. The critical time window for SSD was from 13- to 14-month-old, with females reaching significantly larger sizes than males. Muscle cell size and plasma growth hormone (GH), insulin-like growth factor 1 and 2 (IGF1, IGF2), 11-ketotestosterone (11-KT), and 17β-estradiol (E2) levels had no significant differences between the sexes of 13- and 14-month-old flounders. Furthermore, the RNA-seq data revealed differential expression in the genes encoding the receptors for these hormones, suggesting that regulation may occur at the receptor level, potentially leading to SSD during the critical window. RNA-seq analysis identified 88, 645, 414, and 15,833 differentially expressed genes between females and males in brains/pituitaries, livers, muscles, and gonads, respectively. KEGG (Kyoto Encyclopedia of Genes and Genomes) and GSEA-based KEGG analyses revealed that some pathways associated with growth and development, including “prolactin signaling pathway” in brains/pituitaries, “cell cycle”, “oocyte meiosis”, and “DNA replication” in livers, “focal adhesion”, “ECM-receptor interaction”, “protein digestion and absorption”, “arginine and proline metabolism”, and “cysteine and methionine metabolism” in muscles, and “Hippo signaling pathway” and “JAK-STAT signaling pathway” in gonads may be involved in the establishment of sexual growth differences. Notably, females had lower steroid hormone synthesis abilities than males in brains/pituitaries, livers, and gonads, indicating the importance of sex steroid hormones in the establishment of SSD. Moreover, genes including frizzled3 (fzd3) and prolactin (prl) in brains/pituitaries, and growth hormone receptor (ghr), estrogen receptor (esr1), insulin-like growth factor binding protein-3 (igfbp3), bone morphogenetic protein 8A-like (bmp8a), leptin receptor (lepr), and lipoprotein lipase-like (lpl) in livers emerge as potential candidates for the establishment of SSD. In conclusion, this study may help clarify the molecular mechanisms involved in SSD-related growth traits in flounder and provide basic data for genetic breeding of flounder.

Deficiency of leap2 promotes somatic growth in zebrafish: Involvement of the growth hormone system

PurposeLiver-expressed antimicrobial peptide-2 (LEAP2) is identified as an endogenous antagonist and inverse agonist of the growth hormone secretagogue receptor type 1a (GHSR1a), its effect on the GHSR1a is contrary to the role of GHRELIN. Growth hormone (GH) is a crucial hormone for early development. Previous studies report that LEAP2 dose-dependently attenuates ghrelin-induced GH secretion, and Leap2-knockout mice exhibit increased plasma GH levels after GHRELIN administration. Clinical data revealed a possible correlation between LEAP2 and height development. However, the role of LEAP2 in early development remains unclear. This study aimed to investigate the role of LEAP2 in early development using leap2 mutant zebrafish larvae as a model. MethodWe analyzed the conservation of LEAP2 peptide across multiple species and generated leap2 mutants in zebrafish by CRISPR-Cas9, dynamically observed and measured the growth and development of zebrafish larvae from fertilization to 5 day post fertilization (dpf). In situ hybridization, transcriptome sequencing, quantitative real-time PCR and Western blot were used to detect the expression levels of GH and its signaling in early stage of embryonic development. ResultOur data demonstrate that zebrafish with a knockout of the leap2 gene display a significant increase in hatching rate, body length, and the distance between their eyes, all without visible developmental defects in the early stages of development. In addition, both RNA and protein analyses revealed a significant increase in GH expression in leap2 mutant. ConclusionIn general, this study demonstrates that LEAP2 regulates the expression of GH during early development, particularly influencing body length.

Effects of Intranasal Naloxone on Hypoglycemia-Associated Autonomic Failure (HAAF) in Susceptible Individuals.

Hypoglycemia-associated autonomic failure (HAAF), defined as blunting of counter-regulatory hormone and symptom responses to recurrent hypoglycemia, remains a therapeutic challenge in diabetes treatment. The opioid system may play a role in HAAF pathogenesis since activation of opioid receptors induces HAAF. Blockade of opioid receptors with intravenous naloxone ameliorates HAAF experimentally, yet is not feasible therapeutically. To investigate the effects of opioid receptor blockade with intranasal naloxone on experimentally-induced HAAF. Randomized, double-blinded, placebo-controlled crossover study. Academic research center. Healthy non-diabetic volunteers. Paired two-day studies, 5-10 weeks apart, each consisting of three consecutive hypoglycemic episodes (hyperinsulinemic hypoglycemic clamps, glucose nadir: 54 mg/dL): two on day 1 with administration of intranasal naloxone vs. placebo, followed by the third episode on day 2. Differences in counter-regulatory hormones responses and hypoglycemia symptoms between first and third hypoglycemic episodes in naloxone vs. placebo studies. Out of 17 participants, 9 developed HAAF, confirming variable inter-individual susceptibility. Among participants susceptible to HAAF, naloxone maintained some hormonal and symptomatic responses to hypoglycemia and prevented the associated requirement for increased glucose infusion. Unexpectedly, naloxone reduced plasma epinephrine and growth hormone responses to the first hypoglycemic episode but prevented further reduction with subsequent hypoglycemia. This is the first study to report that intranasal naloxone, a widely used opioid receptor antagonist, may ameliorate some features of HAAF. Further investigation is warranted into mechanisms of variable inter-individual susceptibility to HAAF and the effects of intranasal naloxone in people with diabetes at risk for HAAF.

Effects of heat stress on endocrine, thermoregulatory, and lactation capacity in heat-tolerant and -sensitive dry cows.

Increasing global temperatures present a significant challenge to livestock production. The dry period is an important stage in the production cycle of cow, and environmental heat stress (HS) during this period can have adverse effects on the subsequent lactation performance. In this study, we aimed to investigate the effects of HS on endocrine, thermoregulatory, and lactation parameters in heat-tolerant dry cows (HTDC) and heat-sensitive dry cows (HSDC). We measured the respiratory rate (RR), body temperature (BT), and temperature-humidity index (THI) in 66 dry cows during HS. The slopes of RR and BT to THI were determined through analysis of measurements and dry cows background information using a mixed-effects model. Subsequently, the heat tolerance or sensitivity of dry cows was assessed using clustering method (HTDC = 19 and HSDC = 47). Compared with that of HSDC, the RR of HTDC significantly increased after exposure to HS (p < 0.05). The average reduction in milk yield from new lactation to the previous lactation was significantly lower in HTDC compared to HSDC (p < 0.05). Plasma cortisol and non-esterified fatty acid levels were significantly lower in HTDC compared to HSDC (p < 0.05), while plasma triiodothyronine (p = 0.07) and growth hormone (p = 0.08) levels tended to be higher in HTDC relative to HSDC. HTDC can more effectively alleviate the impacts of HS through their superior thermoregulation and metabolism, thereby ensuring optimal postpartum lactation performance.

Plasma growth hormone as a prognostic biomarker to durvalumab and tremelimumab in patients with advanced hepatocellular carcinoma.

e16161 Background: In this study, we explored the potential of plasma growth hormone (GH) as a prognostic biomarker in patients with advanced HCC treated with durvalumab plus tremelimumab (D+T). Methods: In this study, we included 24 patients with advanced HCC who received D+T at MD Anderson Cancer Center between 2022 and 2023. Plasma GH levels were measured from prospectively collected blood samples from 16 of the 24 patients and were correlated with progression-free survival (PFS) and overall survival (OS). The cutoff for normal GH levels in women and men was defined as ≤3.7 μg/L and ≤0.9 μg/L, respectively. The Kaplan-Meier method was employed to compute the median OS and PFS, while the Log-rank test was applied to compare the survival outcomes between the GH-high and GH-low groups. Results: Twenty-four patients were included in this analysis, four female and twenty male, with a median age of 66.5 years. Of these 24 patients, 16 had GH levels available for analysis. At the time of the analysis, the 6-month OS rate was 100% among GH-low patients (6 patients) and 30% among GH-high patients (10 patients). OS was significantly longer in GH-low patients (not evaluable) compared to GH-high patients (3.94 months) (p = 0.030). PFS was also significantly longer in GH-low patients (not evaluable) compared to the GH-high patients (1.87 months) (p = 0.036). Conclusions: Plasma GH is a prognostic biomarker in patients with advanced HCC treated with D+T. Given the relatively small patient cohort size, this finding should be further validated in larger randomized clinical trials in advanced HCC patients.

Progressive substitution of fish oil with Schizochytrium-derived algal oil in the diet of Atlantic salmon (Salmo salar) parr subjected to winter signal period

The aim of this study was to investigate the impact of progressive replacement of fish oil with Schizochytrium-derived oil from Veramaris® (VMO) in the diets of Atlantic salmon, focusing on its effect during the pre-adaptation to smoltification phase of parr, with an emphasis on the winter signal period. Substitution of fish oil with VMO during this critical developmental phase of salmon (pre-adaptation to smoltification phase) can contribute to the goal of reducing dependence on wild fisheries as a primary source of essential fatty acids in aquafeeds. Three isoproteic, isolipidic and isoenergetic diets were formulated; a control diet containing 5% fish oil and 12% plant oil (0VMO) and two other diets, in which 50% and 100% of the EPA+DHA from fish oil were replaced with VMO, henceforth referred to as 50VMO and 100VMO, respectively. The fish were exposed to a 12 L:12D photoperiod over a 49-day window with samples collected at five time points, including a 48-h salt water challenge to evaluate the effects on common smoltification-related biomarkers including the expression of two genes coding for the two protein isoforms of the NKA alpha catalytic subunit (nkaa1a, nkaa1b), the gene coding for NA+/K+Cl⁻ co-transporter (nkcc1) in the gills as well as osmolality, Cl-, Mg2+, Ca2+, cortisol, growth hormone, and insulin-like growth factor-1 in plasma. The results showed non-significant differences in growth performance and only minor differences in smoltification-related parameters between the dietary treatment groups. Overall, the unconventional source of EPA+DHA was not detrimental to growth, hypoosmoregulatory ability or general welfare, suggesting that the progressive substitution of fish oil with Schizochytrium-derived oil in diets for Atlantic salmon parr is a viable option for adoption by the aquaculture industry.

The relations between serum growth hormone, seminal plasma growth hormone, and sperm count in acromegaly patients

The relations between serum growth hormone, seminal plasma growth hormone, and sperm count in acromegaly patients

Influence of Silicon Supplementation on Growth, Immunity, Antioxidant, Hormonal Profile and Bone Health Biomarkers in Pre-ruminant Crossbred Calves.

Silicon (Si), a newer trace element, is believed to be important for healthy bone formation and to decrease bone resorption, improving the quality of bone by manipulating several hormones and enzymes. Therefore, the current investigation was conducted to determine the impact of Si supplementation on growth, immunity, antioxidant, hormonal profile and biomarkers of bone health in pre-ruminant crossbred calves. Twenty-four crossbred calves (5-7 days) were selected on the basis of their body weight (BW 31.65 ± 0.46 kg) and divided into 4 groups (n = 6) and fed as per ICAR (2013) feeding standards except that these were additionally supplemented with 0 (Si0), 50 (Si50), 100 (Si100) and 150 (Si150) mg of Si/kg dry matter (DM) in four respective groups for 90 days. Every month, peripheral blood samples were drawn (0, 30, 60 and 90 days post supplementing with Si) and analysed for antioxidant status, hormonal profile and bone health biomarkers. It is reported that dietary Si supplementation improved (P < 0.05) net body weight gain (kg), average daily gain (g) and average dry matter intake (kg), whereas feed intake (kg/100 kg BW), was not altered due to Si supplementation. Structural growth measurements were significantly higher (P < 0.05) in Si100 and Si150 groups as compared to Si50 and control groups. However, immune response (humoral as well as cell-mediated immunity), erythrocytic antioxidant enzymes (superoxide dismutase, SOD, glutathione peroxidase, GPx and catalase), plasma ferric reducing total antioxidant power (FRAP) activity and the plasma concentration of total immunoglobulins (TIg) remained unaffected by Si supplementation. Silicon increased (P < 0.05) the concentration of plasma growth hormone (GH), vitamin D3, bone alkaline phosphatase (BALP) and osteocalcin (OCN) in Si100 and Si150 groups, but the levels of calcitonin, parathyroid hormone (PTH) and hydroxyproline (HYP) remained similar among all the groups. As a result of the current investigation, it can be inferred that the inclusion of 100 and 150 mg of Si/kg DM was effective in improving the growth performance, growth hormone, vitamin D3 and bone health status in pre-ruminant calves. However, supplementation of 150 mg of Si/kg DM had no additional benefit; therefore 100 mg of Si/kg DM is the optimum level of Si supplementation in pre-ruminant calves.

Association of an impaired GH-IGF-I axis with cardiac wasting in patients with advanced cancer.

Growth hormone (GH) resistance is characterized by high GH levels but low levels of insulin-like growth factor-I (IGF-I) and growth hormone binding protein (GHBP) and, for patients with chronic disease, is associated with the development of cachexia. We investigated whether GH resistance is associated with changes in left ventricular (LV) mass (cardiac wasting) in patients with cancer. We measured plasma IGF-I, GH, and GHBP in 159 women and 148 men with cancer (83% stage III/IV). Patients were grouped by tertile of echocardiographic LVmass/height2 (women, < 50, 50-61, > 61g/m2; men, < 60, 60-74, > 74g/m2) and by presence of wasting syndrome with unintentional weight loss (BMI < 24kg/m2 and weight loss ≥ 5% in the prior 12months). Repeat echocardiograms were obtained usually within 3-6months for 85 patients. Patients in the lowest LVmass/height2 tertile had higher plasma GH (median (IQR) for 1st, 2nd, and 3rd tertile women, 1.8 (0.9-4.2), 0.8 (0.2-2.2), 0.5 (0.3-1.6) ng/mL, p = 0.029; men, 2.1 (0.8-3.2), 0.6 (0.1-1.7), 0.7 (0.2-1.9) ng/mL, p = 0.003). Among women, lower LVmass was associated with higher plasma IGF-I (68 (48-116), 72 (48-95), 49 (35-76) ng/mL, p = 0.007), whereas such association did not exist for men. Patients with lower LVmass had lower log IGF-I/GH ratio (women, 1.60 ± 0.09, 2.02 ± 0.09, 1.88 ± 0.09, p = 0.004; men, 1.64 ± 0.09, 2.14 ± 0.11, 2.04 ± 0.11, p = 0.002). GHBP was not associated with LVmass. Patients with wasting syndrome with unintentional weight loss had higher plasma GH and GHBP, lower log IGF-I/GH ratio, and similar IGF-I. Overall, GHBP correlated inversely with log IGF-I/GH ratio (women, r = - 0.591, p < 0.001; men, r = - 0.575, p < 0.001). Additionally, higher baseline IGF-I was associated with a decline in LVmass during follow-up (r = - 0.318, p = 0.003). In advanced cancer, reduced LVmass is associated with increased plasma GH and reduced IGF-I/GH ratio, suggesting increasing GH resistance, especially for patients with wasting syndrome with unintentional weight loss. Higher baseline IGF-I was associatedwith a decrease in relative LVmass during follow-up.

Effect of Dietary Vitamin C Supplementation on Growth Performance and Biochemical Parameters in Grower Walleye Pollock, Gadus chalcogrammus.

The optimal dietary vitamin C (VC) levels for walleye pollock (Gadus chalcogrammus) remain undefined. This study aimed to assess the effect of dietary VC levels on the growth performance and biochemical parameters of grower walleye pollock and determine the optimal VC level for their diet. Six experimental diets (VC0, VC1, VC3, VC5, VC7, and VC10) with VC levels of 3.24, 21.92, 63.31, 101.42, 145.46, and 202.51 mg kg-1 diet, respectively, were fed to fish (initial mean weight: 173.5 ± 0.31 g) for 8 weeks. At the end of the feeding trial, fish fed the VC7 and VC10 diets exhibited significantly higher growth (final body weight, weight gain, and specific growth rate) and improved feed utilization (feed efficiency and protein efficiency ratio) compared with fish fed the VC0 diet (p < 0.05). The VC3-VC10 diets significantly reduced plasma superoxide dismutase (SOD) activity (p < 0.05). Compared with the VC0 group, fish fed the VC7 and VC10 diets showed significantly elevated growth hormone and insulin-like growth factor-1 levels in plasma (p < 0.05). In conclusion, dietary VC supplementation in walleye pollock improved growth performance and SOD activity. Moreover, broken-line analysis on weight gain indicated that the optimal dietary VC level for grower walleye pollock was approximately 156.42 mg kg-1 diet.

Effects of dietary pectin on the growth performance, intestinal barrier, and antioxidant status of juvenile rainbow trout (Oncorhynchus mykiss)

To evaluate the effects of dietary pectin on growth performance, intestinal barrier, and antioxidant status of juvenile rainbow trout (Oncorhynchus mykiss), 10-week feeding trial was conducted. Five isoproteic and isoenergetic diets were formulated to contain 0% (P0), 4% (P4), 8% (P8), and 16% (P16) pectin as well as 0.02% pectinase (PE) at the expense of wheat starch, respectively. Dietary inclusion of 416% pectin linearly promoted the feed intake and growth performance but depressed the feed efficiency, but significant differences were only observed between the P16 and P0 groups. Similarly, dietary inclusion of 816% pectin significantly increased the foregut trypsin and amylase activities but decreased the foregut and midgut sucrase activity. The midgut muc2 gene expression level was significantly down-regulated by the inclusion of 16% pectin. Dietary inclusion of 2% pectin increased the abundance of Proteobacteria and Stenotrophomonas but reduced the abundance of Actinobacteria, Bacteroides and Helicobacter; while the lowest values of observed species, Chao1 and ACE indices of intestinal flora were found in the P8 group. Fish fed with the P8 diet exhibited the lowest plasma catalase and midgut glutathione S-transferase activities as well as malondialdehyde content, but the highest midgut malondialdehyde content. Dietary inclusion of 816% pectin significantly depressed the plasma growth hormone (GH), insulin-like growth factor-1 (IGF-1) and mechanistic target of rapamycin contents as well as alanine aminotransferase activity, the hepatic adenosine monophosphate deaminase and glutamate dehydrogenase (GDH) activities. Dietary treatment with 0.02% pectinase did not affect the growth performance, but depressed the foregut sucrase activity, the midgut amylase and sucrase activities, increased the plasma GH and IGF-1 contents as well as hepatic GDH and aspartate aminotransferase activities. In conclusion, high-dose of dietary pectin (816%) may promote the feed intake and intestinal digestive enzyme activities and thereby improve the growth performance of rainbow trout.

Growth Hormone Mediators and Glycemic Control in Youths With Type 2 Diabetes

Youth-onset type 2 diabetes (T2D) has a more aggressive phenotype than adult-onset T2D, including rapid loss of glycemic control and increased complication risk. To identify associations of growth hormone mediators with glycemic failure, beta cell function, and insulin sensitivity in youth-onset T2D. This post hoc secondary analysis of the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) randomized clinical trial, which enrolled participants from July 2004 to February 2009, included 398 participants from 15 university-affiliated medical centers with available plasma samples from baseline and 36 months. Participants were youths aged 10 to 17 years with a duration of T2D of less than 2 years who were randomized to metformin, metformin plus lifestyle intervention, or metformin plus rosiglitazone. Participants were followed up for a mean (SD) of 3.9 (1.5) years during the trial, ending in 2011. Statistical analysis was performed from August 2022 to November 2023. Plasma insulin-like growth factor-1 (IGF-1), growth hormone receptor (GHR), and insulin-like growth factor binding protein 1 (IGFBP-1). Main outcomes were (1) loss of glycemic control during the TODAY study, defined as hemoglobin A1c (HbA1c) level of 8% or more for 6 months or inability to wean from insulin therapy, and (2) baseline and 36-month measures of glycemia (fasting glucose, HbA1c), insulin sensitivity (1/fasting C-peptide), high-molecular-weight adiponectin, and beta cell function (C-peptide index, C-peptide oral disposition index). This analysis included 398 participants (mean [SD] age, 13.9 [2.0] years; 248 girls [62%]; 166 Hispanic participants [42%]; 134 non-Hispanic Black participants [34%], and 84 non-Hispanic White participants [21%]). A greater increase in IGF-1 level between baseline and 36 months was associated with lower odds of glycemic failure (odds ratio [OR], 0.995 [95% CI, 0.991-0.997]; P < .001) and higher C-peptide index per 100-ng/mL increase in IGF-1 (β [SE], 0.015 [0.003]; P < .001). A greater increase in log2 GHR level between baseline and 36 months was associated with higher odds of glycemic failure (OR, 1.75 [95% CI, 1.05-2.99]; P = .04) and lower C-peptide index (β [SE], -0.02 [0.006]; P < .001). A greater increase in log2 IGFBP-1 level between baseline and 36 months was associated with higher odds of glycemic failure (OR, 1.37 [95% CI, 1.09-1.74]; P = .007) and higher high-molecular-weight adiponectin (β [SE], 431 [156]; P = .007). This study suggests that changes in plasma growth hormone mediators are associated with loss of glycemic control in youth-onset T2D, with IGF-1 associated with lower risk and GHR and IGFBP-1 associated with increased risk. ClinicalTrials.gov Identifier: NCT00081328.

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.

Plasma Growth Hormone as a Prognostic Biomarker to Durvalumab and Tremelimumab in Patients with Advanced Hepatocellular Carcinoma.

In this study, we explored the potential of plasma growth hormone (GH) as a prognostic biomarker in patients with advanced HCC treated with durvalumab plus tremelimumab (D+T). In this study, we included 16 patients with advanced HCC who received D+T at MD Anderson Cancer Center between 2022 and 2023 and had plasma GH measurements recorded before treatment. Plasma GH levels were measured from prospectively collected blood samples and were correlated with progression-free survival (PFS) and overall survival (OS). The cutoff for normal GH levels in women and men was defined as ≤3.7 μg/L and ≤0.9 μg/L, respectively. The Kaplan-Meier method was employed to compute the median OS and PFS, while the Log rank test was applied to compare the survival outcomes between the GH-high and GH-low groups. Sixteen patients were included in this analysis, two female and fourteen male, with a median age of 65.5 years. At the time of the analysis, the 6-month OS rate was 100% among GH-low patients (6 patients) and 30% among GH-high patients (10 patients). OS was significantly longer in GH-low patients (not evaluable) compared to GH-high patients (3.94 months) (p = 0.030). PFS was also significantly longer in GH-low patients (not evaluable) compared to the GH-high patients (1.87 months) (p = 0.036). Plasma GH is a prognostic biomarker in patients with advanced HCC treated with D+T. Given the relatively small patient cohort size, this finding should be further validated in larger randomized clinical trials in advanced HCC patients.