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Growth Hormone & IGF Research

Michael J Redd, Jay R Hoffman, Yftach Gepner, Jeffrey R Stout, Mattan W Hoffman, Daniel Ben-Dov, Shany Funk, David D Church, Guy Avital, Yacov Chen, Hagai Frankel, Ishay Ostfeld
OBJECTIVE: Insulin-like growth factor-I (IGF-I) is a metabolic and anabolic biomarker that has been proposed to reflect physiological adaptations resulting from multistressor environments. The bioactivity of IGF-I is regulated by seven different insulin-like growth factor binding proteins (IGFBPs) which act not only as carriers of IGF-1, but also function as a modulator of IGF-I availability and activity. Supplementing with β-hydroxy-β-methylbutyrate (HMB) has been shown to enhance physiological outcomes associated with intense training, and has been reported to augment the IGF-1 response...
October 5, 2016: Growth Hormone & IGF Research
F Maffezzoni, S Frara, M Doga, G Mazziotti, A Giustina
Acromegaly is a rare disease associated with significant morbidity and increased mortality. Treatment of acromegaly aims at controlling growth hormone hypersecretion, improving patients' symptoms and comorbidities and normalizing mortality. The therapeutic options for acromegaly include surgery, medical therapies and radiotherapy. However, despite all these treatment options, approximately one-half of patients are not adequately controlled. Progress in molecular research has made possible to develop new therapeutic strategies to improve control of acromegaly...
October 4, 2016: Growth Hormone & IGF Research
Briony E Forbes
The last two years of insulin-like growth factor (IGF) research has yielded a vast literature highlighting the central role IGFs factors play in processes such as development, growth, aging and neurological function. It also provides our latest understanding of how IGF system perturbation is linked to diseases including growth deficiency, cancer, and neurological and cardiovascular diseases. A snapshot of the highlights is presented in this review, focussing on the topics of IGFs and growth, comparative and structural biology to understand insulin-like peptide function, IGFs and cancer, and IGFs and neurological function...
September 30, 2016: Growth Hormone & IGF Research
Donato Iacovazzo, Márta Korbonits
X-linked acrogigantism (XLAG) is a recently identified condition of early-onset GH excess resulting from the germline or somatic duplication of the GPR101 gene on chromosome Xq26.3. Thirty patients have been formally reported so far. The disease affects mostly females, occurs usually sporadically, and is characterised by early onset and marked overgrowth. Most patients present with concomitant hyperprolactinaemia. Histopathology shows pituitary hyperplasia or pituitary adenoma with or without associated hyperplasia...
September 29, 2016: Growth Hormone & IGF Research
Ann Hellström, David Ley, Ingrid Hansen-Pupp, Boubou Hallberg, Luca A Ramenghi, Chatarina Löfqvist, Lois E H Smith, Anna-Lena Hård
Retinopathy of prematurity is a potentially blinding disease, which is associated with low neonatal IGF-I serum concentrations and poor growth. In severe cases impaired retinal vessel growth is followed by pathologic neovascularization, which may lead to retinal detachment. IGF-I may promote growth even in catabolic states. Treating preterm infants with recombinant human (rh) IGF-I to concentrations normally found during gestation has been suggested to have a preventative effect on ROP. A recent phase 2 study treating infants (gestational age between 23weeks+0days and 27weeks +6days) with rhIGF-I/IGF binding protein-3 until 30 postmenstrual weeks showed no effect on ROP but a 53% reduction in severe bronchopulmonary dysplasia and 44% reduction in severe intraventricular hemorrhage...
September 28, 2016: Growth Hormone & IGF Research
Leon A Bach
IGFBP-6 binds IGF-II with higher affinity than IGF-I and it is a relatively specific inhibitor of IGF-II actions. More recently, IGFBP-6 has also been reported to have IGF-independent effects on cell proliferation, survival, differentiation and migration. IGFBP-6 binds to several ligands in the extracellular space, cytoplasm and nucleus. These interactions, together with activation of distinct intracellular signaling pathways, may contribute to its IGF-independent actions; for example, IGF-independent migration induced by IGFBP-6 involves interaction with prohibitin-2 and activation of MAP kinase pathways...
September 22, 2016: Growth Hormone & IGF Research
Odaly Toffoletto, Jorge Afiune, Josef Ernst Thiemann, Suhas S Khandave, Swati Patel, Debora G Rodrigues
OBJECTIVE: To extend available dosing options in the treatment of growth hormone deficiency, a comparative pharmacokinetic and pharmacodynamic phase-1 clinical study involving subcutaneous administration of growth hormone was conducted. DESIGN: The test formulation (biosimilar recombinant human growth hormone; r-hGH; Somatotropin) and reference formulation (Genotropin®) were tested in 38 adult healthy subjects after their subcutaneous administration of 12.8IU in an open label, single dose, randomized, two period cross over study separated with a washout period of 11days...
September 16, 2016: Growth Hormone & IGF Research
Ronald W Matheny, Christopher T Carrigan, Mary N Abdalla, Alyssa V Geddis, Luis A Leandry, Carlos A Aguilar, Stuart S Hobbs, Maria L Urso
OBJECTIVE: Skeletal muscle regeneration is a complex process involving the coordinated input from multiple stimuli. Of these processes, actions of the insulin-like growth factor-I (IGF-I) and phosphoinositide 3-kinase (PI3K) pathways are vital; however, whether IGF-I or PI3K expression is modified during regeneration relative to initial damage intensity is unknown. The objective of this study was to determine whether mRNA expression of IGF-I/PI3K pathway components was differentially regulated during muscle regeneration in mice in response to traumatic injury induced by freezing of two different durations...
September 14, 2016: Growth Hormone & IGF Research
Emily A Southmayd, Mary Jane De Souza
Bone growth, development, and remodeling are modulated by numerous circulating hormones. Throughout the lifespan, the extent to which each of the hormones impacts bone differs. Understanding the independent and combined impact of these hormones on controlling bone remodeling allows for the development of more informed decision making regarding pharmacology, specifically the use of hormonal medication, at all ages. Endocrine control of bone health in women is largely dictated by the growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis and the hypothalamic-pituitary-ovarian (HPO) axis...
September 13, 2016: Growth Hormone & IGF Research
Nicole E Brooks, Rikke Hjortebjerg, Brooke E Henry, Edward O List, John J Kopchick, Darlene E Berryman
OBJECTIVE: Although growth hormone (GH) and fibroblast growth factor 21 (FGF21) have a reported relationship, FGF21 and its receptor, fibroblast growth factor receptor 1 (FGFR1) and cofactor β-Klotho (KLB), have not been analyzed in chronic states of altered GH action. The objective of this study was to quantify circulating FGF21 and tissue specific expression of Fgf21, Fgfr1, and Klb in mice with modified GH action. Based on previous studies, we hypothesized that bovine GH transgenic (bGH) mice will be FGF21 resistant and GH receptor knockout (GHR-/-) mice will have normal FGF21 action...
August 24, 2016: Growth Hormone & IGF Research
Fady Hannah-Shmouni, Giampaolo Trivellin, Constantine A Stratakis
Gigantism and acromegaly are rare disorders that are caused by excessive GH secretion and/or high levels of its mediator, IGF-1. Gigantism occurs when excess GH or IGF-1 lead to increased linear growth, before the end of puberty and epiphyseal closure. The majority of cases arise from a benign GH-secreting pituitary adenoma, with an incidence of pituitary gigantism and acromegaly of approximately 8 and 11 per million person-years, respectively. Over the past two decades, our increasing understanding of the molecular and genetic etiologies of pituitary gigantism and acromegaly yielded several genetic causes, including multiple endocrine neoplasia type 1 and 4, McCune-Albright syndrome, Carney complex, familial isolated pituitary adenoma, pituitary adenoma association due to defects in familial succinate dehydrogenase genes, and the recently identified X-linked acrogigantism...
August 10, 2016: Growth Hormone & IGF Research
Nurit Ashkenazi, Moti Rosenstock, Hussein Hallak, Merav Bassan, Michele Rasamoelisolo, Jost Leuschner, Doron Shinar
PURPOSE: TV-1106 is a recombinant human albumin genetically fused to growth hormone which is intended to reduce the frequency of injections for GH therapy users. We report the safety, tolerability, pharmacokinetics and pharmacodynamics of repeated subcutaneous injections of TV-1106 in Cynomolgus monkeys. METHOD: Cynomolgus monkeys received four weekly subcutaneous injections of 0, 5, 10 or 20mg/kg TV-1106 and were monitored for safety signals throughout the study...
August 3, 2016: Growth Hormone & IGF Research
Kristy Swiderski, Karen Janet Bernice Martins, Annabel Chee, Jennifer Trieu, Timur Naim, Stefan Martin Gehrig, Dale Michael Baum, Julia Brenmoehl, Luong Chau, René Koopman, Paul Gregorevic, Friedrich Metzger, Andreas Hoeflich, Gordon Stuart Lynch
OBJECTIVE: The insulin-like growth factor binding proteins (IGFBPs) are thought to modulate cell size and homeostasis via IGF-I-dependent and -independent pathways. There is a considerable dearth of information regarding the function of IGFBPs in skeletal muscle, particularly their role in the pathophysiology of Duchenne muscular dystrophy (DMD). In this study we tested the hypothesis that intramuscular IGFBP-2 overexpression would ameliorate the pathology in mdx dystrophic mice. DESIGN: 4week old male C57Bl/10 and mdx mice received a single intramuscular injection of AAV6-empty or AAV6-IGFBP-2 vector into the tibialis anterior muscle...
July 29, 2016: Growth Hormone & IGF Research
Virginia M Pereira-Gurgel, Augusto C N Faro, Roberto Salvatori, Thiago A Chagas, José F Carvalho-Junior, Carla R P Oliveira, Ursula M M Costa, Gustavo B Melo, Ann Hellström, Manuel H Aguiar-Oliveira
OBJECTIVE: Experimental models demonstrate an important role of GH in retinal development. However, the interactions between GH and the neuro-vascularization of the human retina are still not clear. A model of untreated congenital isolated GH deficiency (IGHD) may clarify the actions of GH on the retina. The purpose of this work was to assess the retinal neuro-vascularization in untreated congenital IGHD (cIGHD). DESIGN: In a cross sectional study, we performed an endocrine and ophthalmological assessment of 25 adult cIGHD subjects, homozygous for a null mutation (c...
July 27, 2016: Growth Hormone & IGF Research
Karin Bergen, Kerstin Brismar, Sara Tehrani
INTRODUCTION: Insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 1 (IGFBP-1) play an important role in vascular health. Many patients with type 1 diabetes are medicated with HMG-CoA reductase inhibitors, statins, in order to prevent vascular complications. Yet little is known about the effect of statins on the IGF-1/IGFBP-1 axis in these patients. OBJECTIVES: The aim of this study was to evaluate the effect of atorvastatin treatment on IGF-1 and IGFBP-1 with regards to microvascular function...
August 2016: Growth Hormone & IGF Research
Alessandro Ciresi, Floriana Cicciò, Stefano Radellini, Carla Giordano
OBJECTIVE: GH treatment (GHT) can lead to glucose metabolism impairment through decreased insulin sensitivity and impaired pancreatic β-cell function, which are the two key components of the pathogenesis of diabetes. Therefore, in addition to insulin sensitivity, during GHT it is very important to perform a reliable evaluation of insulin secretion. However, conflicting data exist regarding the insulin secretion in children during GHT. C-peptide provides a more reliable estimate of β-cell function than insulin, but few studies evaluated it during GHT...
August 2016: Growth Hormone & IGF Research
Ian P Hughes, Catherine Choong, Shoshana Rath, Helen Atkinson, Andrew Cotterill, Wayne Cutfield, Paul Hofman, Mark Harris
OBJECTIVE: To investigate growth hormone (GH) treatment and treatment cessation with respect to efficacy and efficiency. To identify factors that best classify or predict cessation type: completed treatment (CT), early cessation (EC), or non-response (NR). DESIGN: Observational study (1990-2013) of the Australian GH Program comparing CT, EC, and NR groups with respect to demographic, clinical, and response criteria. All patients treated for GH deficiency (GHD; 909), short stature and slow growth (SSSG; 2144), and Turner Syndrome (TS; 626) were included...
August 2016: Growth Hormone & IGF Research
Kumi Futawaka, Tetsuya Tagami, Yuki Fukuda, Rie Koyama, Ayaka Nushida, Syoko Nezu, Miyuki Imamoto, Masato Kasahara, Kenji Moriyama
OBJECTIVE: To determine if and how growth hormone (GH) signaling is involved in energy metabolism. DESIGN: We used human embryonic kidney TSA201 cells, human H-EMC-SS chondrosarcoma cells, rat L6 skeletal muscle cells, and murine C2C12 skeletal muscle myoblasts to investigate GH-induced expression of uncoupling protein2 (UCP2) to the GHR/JAK/STAT5 pathway by a combination of a reporter assay, electrophoretic mobility shift assay (EMSA), real-time quantitative PCR, Western blotting...
August 2016: Growth Hormone & IGF Research
Shweta Birla, Rajesh Khadgawat, Viveka P Jyotsna, Vandana Jain, M K Garg, Ashu Seith Bhalla, Arundhati Sharma
OBJECTIVE: Human growth is an elementary process which starts at conception and continues through different stages of development under the influence of growth hormone (GH) secreted by the anterior pituitary gland. Variation affecting the production, release and functional activity of GH leads to growth hormone deficiency (GHD), which is of two types: isolated growth hormone deficiency (IGHD) and combined pituitary hormone deficiency (CPHD). IGHD may result from mutations in GH1 and GHRHR while CPHD is associated with defects in transcription factor genes PROP1, POU1F1 and HESX1...
August 2016: Growth Hormone & IGF Research
Sema Ciftci Dogansen, Ozlem Soyluk Selcukbiricik, Betul Ekiz Bilir, Sema Yarman
OBJECTIVE: Many studies have shown that prolactin (PRL) plays an important role in autoimmune diseases. The aim of this study was to compare the current frequency of autoimmune thyroid disease (ATD) in prolactinomas with another type of functional pituitary adenoma (FPA), somatotrophinoma. Another aim of the study was to evaluate possible factors related to thyroid autoimmunity and the process of ATD in FPAs. METHODS: We retrospectively evaluated the presence of thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb) and thyroid morphologic findings in our patients with FPA (78 with acromegaly and 83 with prolactinoma)...
August 2016: Growth Hormone & IGF Research
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