Growth Hormone Release Research Articles

Probing for peptidic drugs (2-10kDa) in doping control blood samples.

Bioactive peptides with a molecular mass between 2 and 10kDa represent an important class of substances banned in elite sports, which has been recognized with an increasing number and variety of substances by anti-doping organizations. Also, the annually renewed list of prohibited substances of the World Anti-Doping Agency (WADA) explicitly mentions more and more of these peptides, and efficient testing procedures are required. Even under simplified sample preparation conditions, liquid chromatography coupled to high-resolution mass spectrometry (with resolution properties>100,000 full width at half maximum) offers suitable conditions for this task and can therefore be used as an initial testing procedure. In contrast to urine, blood analysis essentially relies on the detection of intact peptide hormones, and the expected concentrations are commonly higher in blood samples than in urine. This facilitates the analysis, and a generic sample preparation by means of mixed-mode solid-phase extraction could be realized in this study. Co-extraction and analysis of several different peptides such as insulins (human, lispro, aspart, glulisine, tresiba, detemir, glargine, bovine insulin and porcine insulin), growth hormone releasing hormones (sermorelin, CJC-1295 and tesamorelin), insulin-like growth factors (long-R3-IGF-I, R3-IGF-I and Des1-3-IGF-I) and mechano growth factors (human MGF and MGF-Goldspink) with criteria that fulfil the requirements of the WADA documents (TD2022 MRPL) for doping controls. The proof of principle was shown by the analysis of post administration samples after treatment with synthetic insulin analogues.

Hypnotic enhancement of slow-wave sleep increases sleep-associated hormone secretion and reduces sympathetic predominance in healthy humans

Sleep is important for normal brain and body functioning, and for this, slow-wave sleep (SWS), the deepest stage of sleep, is assumed to be especially relevant. Previous studies employing methods to enhance SWS have focused on central nervous components of this sleep stage. However, SWS is also characterized by specific changes in the body periphery, which are essential mediators of the health-benefitting effects of sleep. Here we show that enhancing SWS in healthy humans using hypnotic suggestions profoundly affects the two major systems linking the brain with peripheral body functions, i.e., the endocrine and the autonomic nervous systems (ANS). Specifically, hypnotic suggestions presented at the beginning of a 90-min afternoon nap to promote subsequent SWS strongly increased the release of growth hormone (GH) and, to a lesser extent, of prolactin and aldosterone, and shifted the sympathovagal balance towards reduced sympathetic predominance. Thus, the hypnotic suggestions induced a whole-body pattern characteristic of natural SWS. Given that the affected parameters regulate fundamental physiological functions like metabolism, cardiovascular activity, and immunity, our findings open up a wide range of potential applications of hypnotic SWS enhancement, in addition to advancing our knowledge on the physiology of human SWS.

747 Human hair follicles functionally respond to growth hormone and growth hormone-releasing hormone, mimicking the central hypothalamic-pituitary-somatotropic axis

Human scalp hair follicles (HFs) are a major non-classical peripheral site of neurohormone production. However, it is unknown whether human scalp HFs also produce the key hypothalamic-pituitary-somatotropic (HPS) axis neurohormones, its main member growth hormone (GH), and its upstream hypothalamic regulator, GH-releasing hormone (GHRH). To answer this, we treated microdissected human scalp HFs with either human GH (100 or 300 ng/mL), or GHRH (100 or 300 ng/mL), for mRNA by qRT-PCR or protein analysis by quantitative immunohistomorphometry of key HPS axis elements.

The GH/IGF-1 Axis Is Associated With Intrahepatic Lipid Content and Hepatocellular Damage in Overweight/Obesity.

Obesity is a state of relative growth hormone (GH) deficiency, and GH has been identified as a candidate disease-modifying target in nonalcoholic fatty liver disease (NAFLD) because of its lipolytic and anti-inflammatory properties. However, the GH/IGF-1 axis has not been well characterized in NAFLD. We aimed to investigate serum GH and IGF-1 levels in relation to intrahepatic lipid content (IHL) and markers of hepatocellular damage and fibrosis in NAFLD. This cross-sectional study included 102 adults (43% women; age 19-67; BMI ≥ 25 kg/m2) without type 2 diabetes. IHL was measured by magnetic resonance spectroscopy; NAFLD was defined by ≥ 5% IHL. Peak-stimulated GH in response to GH releasing hormone and arginine was assessed as was serum IGF-1 (LC/MS). There was no difference in mean age, BMI, or sex distribution in NAFLD vs controls. Mean (± SD) IHL was higher in NAFLD vs controls (21.8 ± 13.3% vs 2.9 ± 1.1%, P < 0.0001). Mean peak-stimulated GH was lower in NAFLD vs controls (9.0 ± 6.3 vs 15.4 ± 11.2 ng/mL, P = 0.003), including after controlling for age, sex, visceral adipose tissue, and fasting glucose. In a stepwise model, peak-stimulated GH predicted 14.6% of the variability in IHL (P = 0.004). Higher peak-stimulated GH was also associated with lower ALT. Higher serum IGF-1 levels were associated with lower risk of liver fibrosis by Fibrosis-4 scores. Individuals with NAFLD have lower peak-stimulated GH levels but similar IGF-1 levels as compared to controls. Higher peak-stimulated GH levels are associated with lower IHL and less hepatocellular damage. Higher IGF-1 levels are associated with more favorable fibrosis risk scores. These data implicate GH and IGF-1 as potential disease modifiers in the development and progression of NAFLD.

Binding Domain Characterization of Growth Hormone Secretagogue Receptor.

Background and ObjectivesActivation of ghrelin receptor growth hormone secretagogue receptor (GHS-R) by endogenous or synthetic ligands amplifies pulsatile release of growth hormone (GH) and enhances food intake, very relevant to development and growth. GHS-R is a G-protein coupled receptor that has great druggable potential. Understanding the precise ligand and receptor interactions is crucial to advance the application of GHS-R.Materials and MethodsWe used radiolabeled ligand-binding assay and growth hormone release assay to assess the binding and functional characteristics of GHS-R to synthetic agonists MK-0677 and GHS-25, as well as to endogenous peptide ligand ghrelin. We analyzed the ligand-dependent activity of GHS-R by measuring aequorin-based [Ca++]i responses. To define a ligand-binding pocket of GHS-R, we generated a series of human/puffer fish GHS-R chimeras by domain swapping, as well as a series of mutants by site-directed mutagenesis.ResultsWe found that the synthetic ligands have high binding affinity to GHS-R in the in vitro competitive binding assay. Remarkably, the in vivo GH secretagogue activity is higher with the synthetic agonists MK-0677 and GHS-25 than that of ghrelin. Importantly, the activity was completely abolished in GHS-R knockout mice. In GHS-R chimera analysis, we identified the C-terminal region, particularly the transmembrane domain 6 (TM6), to be critical for the ligand-dependent activity. Our site-directed mutagenesis study further revealed that amino acid residues D99 and W276 in GHS-R are essential for ligand binding. Interestingly, critical residues distinctively interact with different ligands, MK-0677 activation depends on E124, while ghrelin and GHS-25 preferentially interact with F279.ConclusionThe ligand-binding pocket of human GHS-R is mainly defined by interactive residues in TM6 and the adjacent region of the receptor. This novel finding in GHS-R binding domains advances the structural/ functional understanding of GHS-R, which will help to select/design better GHS-R agonists/ antagonists for future therapeutic applications.

Growth hormone secretagogue peptide A233 upregulates Mx expression in teleost fish in vitro and in vivo.

Aquaculture constitutes an alternative source for food production and contributes to a reduction in the indiscriminate catching of aquatic organisms in their natural environment. However, high mortality during the larval state remains a challenge in this sector, mainly because of factors such as diet and diseases caused by pathogens. Therefore, growth and health management is a key strategy for sustainable aquaculture. Synthetic growth hormone secretagogues (GHSs) are a family of ligands that can stimulate pituitary growth hormone release as well as the function of ghrelin, contributing to the immune responses in a variety of vertebrates, including fish. The A233 decapeptide is a GHS with a demonstrated impact on growth, immune system function, and antioxidant defense in tilapia fish, but no antiviral activity has been described for this peptide. Here, using an in vitro model (TRG-2 cells) and two in vivo models (sea bream [Sparus aurata]) and zebrafish [Danio rerio]), we demonstrate for the first time the potential antiviral effect of A233 in teleost fish.

Polymorphisms of the Growth Hormone Releasing Hormone Receptor Gene Affect Body Conformation Traits in Chinese Dabieshan Cattle.

Simple SummaryIncreasing growth traits can impact the economic benefit of livestock. Polymorphisms can offer us potential molecular markers for the growth traits of cattle, and provide a reference for cultivating an improved cattle population according to the markers in the future. In this study, the growth hormone-releasing hormone receptor gene polymorphism is significantly associated with the body conformation traits of Chinese Dabieshan cattle, and it could be used as a candidate genetic marker for body conformation trait selection in cattle. This study further verified that the GHRHR gene plays a vital role in Chinese cattle, and provides a data basis for the research and improvement of cattle breeding programs in China.This study was performed to expose the polymorphisms of the growth hormone-releasing hormone receptor gene in Chinese Dabieshan cattle, evaluate its effect on body conformation traits, and find potential molecular markers in Chinese cattle. The GHRHR structure and the phylogenetic tree were analyzed using bioinformatics software. The polymorphism of the GHRHR gene in 486 female cattle was genotyped by PCR-RFLP and DNA sequencing, and the association between SNPs and body conformation traits of Chinese Dabieshan cattle was analyzed by one-way ANOVA in SPSS software. GHRHR was often conserved in nine species, and its sequence of cattle was closest to sheep and goats. Six polymorphic SNPs were identified, g.10667A > C and g.10670A > C were missense mutation. The association analysis indicated that the six SNPs significantly influenced the body conformation traits of Chinese Dabieshan cattle (p < 0.05). Six haplotypes were identified and Hap1 (-CAACGA-) had the highest frequency (36.10%). The Hap3/5 (-GCCCCCGGAAGG-) exhibited a significantly greater wither height (WH), hip height (HH), heart girth (HG), and hip width (HW) (p < 0.05). Overall, the polymorphisms of GHRHR affected the body conformation traits of Chinese Dabieshan cattle, and the GHRHR gene could be used as a molecular marker in Dabieshan cattle breeding programs.

Synthetic growth hormone-releasing hormone agonist ameliorates the myocardial pathophysiology characteristic of heart failure with preserved ejection fraction.

To test the hypothesis that the activation of the growth hormone-releasing hormone (GHRH) receptor signalling pathway within the myocardium both prevents and reverses diastolic dysfunction and pathophysiologic features consistent with heart failure with preserved ejection fraction (HFpEF). Impaired myocardial relaxation, fibrosis, and ventricular stiffness, among other multi-organ morbidities, characterize the phenotype underlying the HFpEF syndrome. Despite the rapidly increasing prevalence of HFpEF, few effective therapies have emerged. Synthetic agonists of the GHRH receptors reduce myocardial fibrosis, cardiomyocyte hypertrophy, and improve performance in animal models of ischaemic cardiomyopathy, independently of the growth hormone axis. CD1 mice received 4- or 8-week continuous infusion of angiotensin-II (Ang-II) to generate a phenotype with several features consistent with HFpEF. Mice were administered either vehicle or a potent synthetic agonist of GHRH, MR-356 for 4-weeks beginning concurrently or 4-weeks following the initiation of Ang-II infusion. Ang-II-treated animals exhibited diastolic dysfunction, ventricular hypertrophy, interstitial fibrosis, and normal ejection fraction. Cardiomyocytes isolated from these animals exhibited incomplete relaxation, depressed contractile responses, altered myofibrillar protein phosphorylation, and disturbed calcium handling mechanisms (ex vivo). MR-356 both prevented and reversed the development of the pathological phenotype in vivo and ex vivo. Activation of the GHRH receptors increased cAMP and cGMP in cardiomyocytes isolated from control animals but only cAMP in cardiac fibroblasts, suggesting that GHRH-A exert differential effects on cardiomyocytes and fibroblasts. These findings indicate that the GHRH receptor signalling pathway(s) represents a new molecular target to counteract dysfunctional cardiomyocyte relaxation by targeting myofilament phosphorylation and fibrosis. Accordingly, activation of GHRH receptors with potent, synthetic GHRH agonists may provide a novel therapeutic approach to management of the myocardial alterations associated with the HFpEF syndrome.

Abstract 5317: A novel approach to the treatment of ATRA/ATO resistant acute promyelocytic leukemia

Abstract Acute Promyelocytic Leukemia (APL) is characterized by proliferation of immature promyelocytes. Combination therapy using retinoic acid (RA) and arsenic trioxide (ATO) is considered standard treatment in the clinical environment. Resistance to both RA and ATO is associated with an increased risk of mortality. In addition, relapse occurs in approximately 10-20% of patients undergoing treatment for APL. Growth Hormone Releasing Hormone (GHRH) is a hypothalamic peptide that stimulates the release of Growth Hormone from the anterior pituitary. Our previous studies have demonstrated that human AML cell lines (K-562, THP-1, and KG-1a) display the GHRH receptor (GHRH-R). Incubation with GHRH-R antagonist MIA-602, inhibited proliferation and induced apoptosis. The purpose of this study is to examine the effects of GHRH-R antagonist MIA-602, on the NB4 Human Promyelocytic Leukemia cell line and its ATRA and ATO resistant sub-clone. NB4 cells expressed both GHRH-R and SV1 variants via western blot analysis. Wild type NB4 cells, as well as NB4 cells resistant to both ATRA and ATO (NB4-RAA), were cultured in suspension in RPMI and 10% fetal calf serum. NB4-RAA were established in Dr. Jimenez's lab from the wild type NB4 parent cell line. NB4 and NB4-RAA were plated in triplicate on multi-wells at 50,000 cells/mL. Cell lysates were prepared after incubation with 0.05-5 µmol/L of MIA-602. Cell viability was measured at 24 and 48h. Flow cytometry was also performed on the naïve NB4 parent cell line in addition to NB4-RAA to assess expression of CD-56 the cell surface marker. Upregulation of CD-56, also known as Neural cell adhesion molecule 1 (NCAM-1), has been shown to confer drug resistance in AML and is an important prognostic marker in APL. The viability of both cell lines decreased to similar levels at 24 h and 48 h when exposed to concentrations of MIA-602 higher than 0.05 μmol/L (p &amp;lt; 0.05). A significant decrease in cell viability was seen above 0.5 μmol/L after 48h. No viable cells were found in either cell line after 48h when exposed to 5 μmol/L of MIA-602. No difference in cell viability was found between naïve NB4 and resistant NB4-RAA when exposed to the same concentrations of MIA-602. MIA-602 induced significant changes in the expression level of many death-related genes including CASP9 (&amp;gt;1.5-fold; P&amp;lt;0.05). Results of flow cytometry revealed significantly increased expression of CD-56 (&amp;gt;5.8-fold; p,0.05) in NB4-RAA cells as compared to the parent cell line. These results indicate that resistance to ATRA and ATO in APL cells does not confer subsequent resistance to MIA-602. As a result, MIA-602 targets a pathway that is distinct from that of ATRA &amp; ATO. More importantly, upregulation of pro-apoptotic genes by MIA-602 indicates an alternative pathway elicited by the GHRH-R antagonist in the setting of resistant APL cells. Our results indicate that the resistance to frontline APL therapy can be effectively overcome by using MIA-602. Citation Format: Ravinder S. Chale, Stephanie M. Almeida, Ivan Jozic, Andrew V. Schally, Joaquin J. Jimenez. A novel approach to the treatment of ATRA/ATO resistant acute promyelocytic leukemia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5317.

Acromegaly Caused by Ectopic Growth Hormone Releasing Hormone Secretion: A Review.

IntroductionEctopic acromegaly is a rare condition caused most frequently by growth hormone releasing hormone (GHRH) secretion from neuroendocrine tumors. The diagnosis is often difficult to establish as its main symptoms do not differ from those of acromegaly of pituitary origin.ObjectivesTo determine most common clinical features and diagnostic challenges in ectopic acromegaly.Patients and MethodsA search for ectopic acromegaly cases available in literature was performed using PubMed, Cochrane, and MEDline database. In this article, 127 cases of ectopic acromegaly described after GHRH isolation in 1982 are comprehensively reviewed, along with a summary of current state of knowledge on its clinical features, diagnostic methods, and treatment modalities. The most important data were compiled and compared in the tables.ResultsNeuroendocrine tumors were confirmed in 119 out of 121 patients with histopathological evaluation, mostly of lung and pancreatic origin. Clinical manifestation comprise symptoms associated with pituitary hyperplasia, such as headache or visual field disturbances, as well as typical signs of acromegaly. Other endocrinopathies may also be present depending on the tumor type. Definitive diagnosis of ectopic acromegaly requires confirmation of GHRH secretion from a tumor using either histopathological methods or GHRH plasma concentration assessment. Hormonal evaluation was available for 84 patients (66%) and histopathological confirmation for 99 cases (78%). Complete tumor resection was the main treatment method for most patients as it is a treatment of choice due to its highest effectiveness. When not feasible, somatostatin receptor ligands (SRL) therapy is the preferred treatment option. Prognosis is relatively favorable for neuroendocrine GHRH-secreting tumors with high survival rate.ConclusionAlthough ectopic acromegaly remains a rare disease, one should be aware of it as a possible differential diagnosis in patients presenting with additional symptoms or those not responding to classic treatment of acromegaly.

Clinical Usefulness of the Growth Hormone-Releasing Peptide-2 Test for Hypothalamic-Pituitary Disorder.

ContextGrowth hormone deficiency (GHD) develops early in patients with hypothalamic-pituitary disorder and is frequently accompanied by other anterior pituitary hormone deficiencies, including secondary adrenal insufficiency (AI). A growth hormone–releasing peptide-2 (GHRP2) test, which is widely used for the diagnosis of patients with GHD, is thought to induce release of not only growth hormone (GH) but also ACTH. However, its clinical usefulness in hypothalamic-pituitary disorder is unclear.ObjectiveWe aimed to determine the clinical utility of the GHRP2 test in patients with hypothalamic-pituitary disorders, particularly for AI concomitant with GHD.MethodsThe GHRP2 test, a cosyntropin stimulation test, corticotropin-releasing hormone (CRH) tests, and/or insulin tolerance tests (ITTs) were performed on 36 patients with hypothalamic-pituitary disorder.ResultsTwenty-two (61%) had severe GHD, and 3 (8%) had moderate GHD by GHRP2. There was no difference in baseline ACTH and cortisol between non-GHD, moderate GHD, and severe GHD participants. However, a cosyntropin stimulation test and subsequent CRH tests and/or ITTs revealed that 17 (47%) had secondary AI and 16/17 (94%) cases of secondary AI were concomitant with severe GHD. ROC curve analysis demonstrated that the ACTH response in the GHRP2 test was useful for screening pituitary-AI, with a cutoff value of 1.55-fold (83% sensitivity and 88% specificity). Notably, the combination of ACTH response and the peak cortisol level in the GHRP2 test using each cutoff value (1.55-fold and 10 µg/dL, respectively) showed high specificity (100%) with high accuracy (0.94) for diagnosis of pituitary-AI.ConclusionWe recommend measuring ACTH as well as GH during the GHRP2 test to avoid overlooking or delaying diagnosis of secondary AI that frequently accompanies GHD.

The protective role of exogenous Ghrelin versus its combination with Zingerone on experimentally induced gastric ischemic-reperfusion in adult male albino rats.

Ghrelin is a gut hormone has stimulatory properties on food intake, fat deposition and growth hormone release. Zingerone is a component of ginger with multiple pharmacological activities. They were established that have protective roles against oxidative stress actions. We planned this study to evaluate pretreatment exogenous Ghrelin alone and or accompanied with Zingerone on ischemia-reperfusion injury to gastric fundus wall. Fifty male albino rats were used and subdivided into control, ischemic- reperfusion, Ghrelin pretreated and Ghrelin Zingerone pretreated groups. Specimens from the stomach fundus were processed for histological, immunohistochemical study and gene expression using real time PCR. Morphometric and statistical analyses were also carried out in this research. In ischemic-reperfusion sections, there were deep erosion and distortion of the mucosa. Chief cells appeared with vacuolated cytoplasm and pyknotic nuclei. Congestion of blood vessels with extravasation and cellular infiltration was also noticed. There was a decrease in mucous secreted cells in PAS-stained sections. Sections from Ghrelin pretreated and Ghrelin Zingerone pretreated groups showed a great improvement. In addition, gastric tissues with the ischemia-reperfusion group showed a significant decrease in enos and nrf2 mRNA expression while there was a significant increase in HIF and VEGF, which is counteracted to Ghrelin pretreated and Ghrelin Zingerone pretreated groups. This study revealed the vital protective role of Ghrelin in concomitant with Zingerone than pretreated Ghrelin alone on attenuating the damage changes of fundus that occurred after experimentally induced gastric ischemia-reperfusion.

The protective role of exogenous Ghrelin versus its combination with Zingerone on experimentally induced gastric ischemic-reperfusion in adult male albino rats

Ghrelin is a gut hormone has stimulatory properties on food intake, fat deposition and growth hormone release. Zingerone is a component of ginger with multiple pharmacological activities. They were established that have protective roles against oxidative stress actions. We planned this study to evaluate pretreatment exogenous Ghrelin alone and or accompanied with Zingerone on ischemia-reperfusion injury to gastric fundus wall. Fifty male albino rats were used and subdivided into control, ischemic- reperfusion, Ghrelin pretreated and Ghrelin Zingerone pretreated groups. Specimens from the stomach fundus were processed for histological, immunohistochemical study and gene expression using real time PCR. Morphometric and statistical analyses were also carried out in this research. In ischemic-reperfusion sections, there were deep erosion and distortion of the mucosa. Chief cells appeared with vacuolated cytoplasm and pyknotic nuclei. Congestion of blood vessels with extravasation and cellular infiltration was also noticed. There was a decrease in mucous secreted cells in PAS-stained sections. Sections from Ghrelin pretreated and Ghrelin Zingerone pretreated groups showed a great improvement. In addition, gastric tissues with the ischemia-reperfusion group showed a significant decrease in enos and nrf2 mRNA expression while there was a significant increase in HIF and VEGF, which is counteracted to Ghrelin pretreated and Ghrelin Zingerone pretreated groups. This study revealed the vital protective role of Ghrelin in concomitant with Zingerone than pretreated Ghrelin alone on attenuating the damage changes of fundus that occurred after experimentally induced gastric ischemia-reperfusion.

Unfolded protein response in endothelial injury

ABSTRACT Endothelial barrier dysfunction is associated with sepsis and lung injury, both direct and indirect. We discuss the involvement of unfolded protein response in the protective effects of heat shock protein 90 inhibitors and growth hormone releasing hormone antagonists in the vascular barrier, to reveal new possibilities in acute respiratory distress syndrome treatment.

Ghrelin's effects on growth hormone release: to pulse or not to pulse?

Ghrelin's effects on growth hormone release: to pulse or not to pulse?

An interaction between growth hormone/insulin-like growth factor-1 and vitamin D in children with short stature

There are disorders in the growth hormone (GH)/growth factors system in a significant part of patients with short stature; first of all, this concerns such diseases as growth hormone deficiency, where there is a sharp decrease in GH, insulin-like growth factor-1 (IGF-1). The association between vitamin D and GH/growth factor system remains unclear. It was found that vitamin D is able to increase IGF-1 level in healthy individuals. Linear growth is accelerated after treatment of vitamin D deficiency in children, which may indicate the linking role of vitamin D between the proliferative cells of the growth plate cartilage and GH/growth factor system.Research objective: to determine 25-hydroxyvitamin D level in blood plasma in children with short stature, depending on the state of GH/IGF-1 system.Materials and methods. Study included 101 children with short stature: 33 children with partial somatotropic insufficiency (group 1); 44 children with complete somatotropic insufficiency (group 2); 24 children with syndrome of biologically inactive GH (group 3). Patients in groups 1 and 2 had a confirmed GH deficiency and a decrease or sharp decrease in of IGF-1 level; patients in group 3 had a normal stimulated release of GH against the background of a reduced IGF-1 level. GH, IGF-1, 25-hydroxyvitamin D, thyroid-stimulating hormone, and free thyroxine were determined in all children.Results. The average level of vitamin D in three groups corresponded to the vitamin deficiency according to international standards and was 52.24 ± 5.99 nmol/l in patients with partial somatotropic insufficiency, 67.6 ± 5.35 nmol/l in patients with complete somatotropic insufficiency and 58, ± 7.91 nmol/l in patients with syndrome of biologically inactive GH. A direct correlation was found between vitamin D and background GH level, stimulated GH level in children with both partial and complete somatotropic insufficiency. A direct correlation between vitamin D and IGF-1 level in this group of patients was also detected.Conclusions. It is advisable to determine the serum 25(OH)D in all children with short stature. Vitamin D levels should be taken into account in insulin/clonidine diagnostic tests in order to obtain a realistic indication of stimulated GH and IGF-1 levels.

Glucagon-stimulated copeptin measurements in the differential diagnosis of diabetes insipidus: a double-blind, randomized, placebo-controlled study.

The differential diagnosis of diabetes insipidus is challenging. The most reliable approaches are copeptin measurements after hypertonic saline infusion or arginine, which is a known growth hormone secretagogue but has recently also been shown to stimulate the neurohypophysis. Similar to arginine, glucagon stimulates growth hormone release, but its effect on the neurohypophysis is poorly studied. Double-blind, randomized, placebo-controlled trial including 22 healthy participants, 10 patients with central diabetes insipidus, and 10 patients with primary polydipsia at the University Hospital Basel, Switzerland. Each participant underwent the glucagon test (s.c. injection of 1 mg glucagon) and placebo test. The primary objective was to determine whether glucagon stimulates copeptin and to explore whether the copeptin response differentiates between diabetes insipidus and primary polydipsia. Copeptin levels were measured at baseline, 30, 60, 90, 120, 150, and 180 min after injection. In healthy participants, glucagon stimulated copeptin with a median increase of 7.56 (2.38; 28.03) pmol/L, while placebo had no effect (0.10 pmol/L (-0.70; 0.68); P < 0.001). In patients with diabetes insipidus, copeptin showed no relevant increase upon glucagon, with an increase of 0.55 (0.21; 1.65) pmol/L, whereas copeptin was stimulated in patients with primary polydipsia with an increase of 15.70 (5.99; 24.39) pmol/L. Using a copeptin cut-off level of 4.6pmol/L had a sensitivity of 100% (95% CI: 100-100) and a specificity of 90% (95% CI: 70-100) to discriminate between diabetes insipidus and primary polydipsia. Glucagon stimulates the neurohypophysis, and glucagon-stimulated copeptin has the potential for a safe, novel, and precise test in the differential diagnosis of diabetes insipidus.

Growth hormone-releasing hormone (GHRH) promotes survival and proliferation of neural stem cells and reduces amyloid-[beta]-induced toxicity

Growth hormone-releasing hormone (GHRH) promotes survival and proliferation of neural stem cells and reduces amyloid-[beta]-induced toxicity

Antagonist of growth hormone-releasing hormone (GHRH) potentiates the antitumor effect of chemotherapy in human malignant pleural mesothelioma

Antagonist of growth hormone-releasing hormone (GHRH) potentiates the antitumor effect of chemotherapy in human malignant pleural mesothelioma

Antagonist of growth hormone-releasing hormone (GHRH) inhibits SARS-CoV-2 Spike protein-induced inflammation in macrophages and PBMCs

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)