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14 results on '"MESH: Human Growth Hormone"'

1. Contribution of functionally assessed GHRHR mutations to idiopathic isolated growth hormone deficiency in patients without GH1 mutations

Author

Merih Berberoğlu, Régis Coutant, Şenay Savaş Erdeve, Cécile Brachet, Caroline Thalassinos, Frédéric Brioude, Michel Polak, Erdal Kurnaz, Sabrina Belkacem, Claudine Heinrichs, Aude Soleyan, Zeynep Şıklar, Nathalie Collot, Philippe Chanson, Jean-Claude Carel, Zehra Aycan, Marie-Laure Sobrier, Serge Amselem, Géraldine Viot, Noureddine Kaffel, Stanislas Lyonnet, Philippe Duquesnoy, Eliane Khallouf, Marie Legendre, Enzo Cohen, Soumeya Fedala, Sophie Rose, Florence Dastot, Frédérique Gatelais, Maladies génétiques d'expression pédiatrique [CHU Trousseau] (Inserm U933), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Lamine Debaghine [Alger, Algérie] (HLD), Centre Hospitalier Universitaire Bab El Oued [Alger, Algérie] (CHU Bab El Oued), UF de Génétique moléculaire [CHU Trousseau], CHU Trousseau [APHP], Hôtel-Dieu de France (HDF), Université Saint-Joseph de Beyrouth (USJ), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpitaux Universitaires Paris Centre (CHU Paris Centre), Hôpital Robert Debré, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Signalisation Hormonale, Physiopathologie Endocrinienne et Métabolique, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hôpital Universitaire des Enfants Reine Fabiola [Brussels, Belgium]. (HUERF), Complexe Médical Multidisciplinaire [Sfax, Tunisia] (C2M), Ankara University School of Medicine [Turkey], Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Université Paris Descartes - Paris 5 (UPD5), Université Sorbonne Paris Cité (USPC), Dupuis, Christine, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie des maladies génétiques d'expression pédiatrique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Service de Génétique [Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], AP-HP Hôpital universitaire Robert-Debré [Paris], Hôpital Universitaire des Enfants Reine Fabiola, Université libre de Bruxelles (ULB), Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Division of Paediatric Endocrinology, Dr Sami Ulus Woman Health, Children Research Hospital, Service de Génétique Médicale [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Children's University Hospital Queen Fabiola [Bruxelles, Belgium], Physiopathologie des maladies génétiques d'expression pédiatrique (UMRS_933), and Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, Receptors, Neuropeptide, [SDV]Life Sciences [q-bio], DNA Mutational Analysis, MESH: Amino Acid Sequence, medicine.disease_cause, molecular epidemiology, MESH: Genotype, Exon, Receptors, Pituitary Hormone-Regulating Hormone, Cyclic AMP, IGHD, MESH: Human Growth Hormone, Missense mutation, MESH: DNA Mutational Analysis, Idiopathic Isolated Growth Hormone Deficiency, Genetics (clinical), genotype‐phenotype correlation, MESH: Cyclic AMP, MESH: Genetic Association Studies, Genetics, 0303 health sciences, Mutation, Human Growth Hormone, MESH: Receptors, Neuropeptide, 030305 genetics & heredity, MESH: Genetic Predisposition to Disease, MESH: Amino Acid Substitution, Pedigree, 3. Good health, [SDV] Life Sciences [q-bio], functional studies, Female, MESH: Mutation, Genotype, MESH: Pedigree, Genetic counseling, GHRHR, Biology, genotype-phenotype correlation, MESH: Dwarfism, Pituitary, 03 medical and health sciences, medicine, Humans, Genetic Predisposition to Disease, Amino Acid Sequence, Dwarfism, Pituitary, Gene, Alleles, Genetic Association Studies, 030304 developmental biology, MESH: Humans, Molecular epidemiology, MESH: Receptors, Pituitary Hormone-Regulating Hormone, MESH: Alleles, MESH: Male, Amino Acid Substitution, MESH: Female
Abstract

International audience; Isolated growth hormone deficiency (IGHD) is a rare condition mainly caused by mutations in GH1. The aim of this study was to assess the contribution of GHRHR mutations to IGHD in an unusually large group of patients. All GHRHR coding exons and flanking intronic regions were sequenced in 312 unrelated patients with nonsyndromic IGHD. Functional consequences of all newly identified missense variants were assessed in vitro (i.e., study of the expression of recombinant GHRHRs and their ability to activate the cyclic adenosine monophosphate (cAMP) signaling pathway). Genotype-phenotype correlation analyses were performed according to the nature of the identified mutation. We identified 20 different disease-causing GHRHR mutations (truncating and missense loss-of-function mutations), among which 15 are novel, in 24 unrelated patients. Of note, about half (13/24) of those patients represent sporadic cases. The clinical phenotype of patients with at least one missense GHRHR mutation was found to be indistinguishable from that of patients with bi-allelic truncating mutations. This study, which unveils disease-causing GHRHR mutations in 8% (24/312) of IGHD cases, identifies GHRHR as the second IGHD gene most frequently involved after GH1. The finding that 8% of IGHD cases without GH1 mutations are explained by GHRHR molecular defects (including missense mutations), together with the high proportion of sporadic cases among those patients, has important implications for genetic counseling.

Published
2019
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2. Diagnosis and management of Silver-Russell syndrome: first international consensus statement

Author

Frédéric Brioude, I. Karen Temple, Jet Bliek, Adda Grimberg, Thomas Eggermann, Gudrun E. Moore, Agnès Linglart, Klaus Mohnike, Zeynep Tümer, Edith Said, Ana Pinheiro Machado Canton, Renuka P Dias, Oluwakemi Lokulo-Sodipe, Madeleine D. Harbison, Meropi Toumba, Gerhard Binder, Béatrice Dubern, Anita C. S. Hokken-Koelega, Jennifer Salem, Deborah J G Mackay, Susan M. O’Connell, Miriam Elbracht, Irène Netchine, Justin H Davies, David Monk, Silvia Russo, Emma Wakeling, Mohamad Maghnie, Isabelle Oliver Petit, Krystyna H. Chrzanowska, Eloise Giabicani, Philip Murray, Masayo Kagami, Alexander A. L. Jorge, Tsutomu Ogata, Karen Grønskov, Pediatrics, North West london hospitals NHS Trust, Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), MAGIC Foundation, Department of Clinical Genetics, University of Amsterdam [Amsterdam] (UvA), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Recherche en Epidémiologie Nutritionnelle (UREN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Cité (USPC)-Université Paris 13 (UP13)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut National de la Recherche Agronomique (INRA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU), Clinical genetic clinic, Copenhagen University Hospital, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Service d'endocrinologie pédiatrique [CHU Bicêtre], Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Fetal Growth and Developmental Group, University College of London [London] (UCL), Department of Endocrinology and Metabolism, National Research Institute for Child Health and Development, Department of Pediatrics and Medical Genetics, St. Luke's Hospital, Service de néphrologie et pédiatrie générale [CHU Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Icahn School of Medicine at Mount Sinai [New York] (MSSM), Human Genetics and Genomic Medicine group, Faculty of Medicine, Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], and Human Genetics

Subjects
0301 basic medicine, medicine.medical_specialty, Pediatrics, Internationality, Endocrinology, Diabetes and Metabolism, Gonadotropin-Releasing Hormone/therapeutic use, Human Growth Hormone/therapeutic use, MESH: Disease Management, law.invention, Gonadotropin-Releasing Hormone, 03 medical and health sciences, Endocrinology, Randomized controlled trial, law, Internal medicine, MESH: Gonadotropin-Releasing Hormone, medicine, MESH: Human Growth Hormone, Humans, Silver-Russell Syndrome/diagnosis, Motor skill, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, MESH: Humans, Human Growth Hormone, business.industry, Adrenarche, Disease Management, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, medicine.disease, 3. Good health, Diabetes and Metabolism, Growth hormone treatment, Natural history, Silver-Russell Syndrome, 030104 developmental biology, MESH: Silver-Russell Syndrome, Speech delay, MESH: Internationality, Small for gestational age, medicine.symptom, business, Psychosocial
Abstract

International audience; This Consensus Statement summarizes recommendations for clinical diagnosis, investigation and management of patients with Silver-Russell syndrome (SRS), an imprinting disorder that causes prenatal and postnatal growth retardation. Considerable overlap exists between the care of individuals born small for gestational age and those with SRS. However, many specific management issues exist and evidence from controlled trials remains limited. SRS is primarily a clinical diagnosis; however, molecular testing enables confirmation of the clinical diagnosis and defines the subtype. A 'normal' result from a molecular test does not exclude the diagnosis of SRS. The management of children with SRS requires an experienced, multidisciplinary approach. Specific issues include growth failure, severe feeding difficulties, gastrointestinal problems, hypoglycaemia, body asymmetry, scoliosis, motor and speech delay and psychosocial challenges. An early emphasis on adequate nutritional status is important, with awareness that rapid postnatal weight gain might lead to subsequent increased risk of metabolic disorders. The benefits of treating patients with SRS with growth hormone include improved body composition, motor development and appetite, reduced risk of hypoglycaemia and increased height. Clinicians should be aware of possible premature adrenarche, fairly early and rapid central puberty and insulin resistance. Treatment with gonadotropin-releasing hormone analogues can delay progression of central puberty and preserve adult height potential. Long-term follow up is essential to determine the natural history and optimal management in adulthood.

Published
2017
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3. Truncation of PITX2 differentially affects its activity on physiological targets

Author

Véronique Vieira, Maurice Menasche, James P. Herman, Thierry Brue, Alain Enjalbert, Marc Abitbol, Marie-Helene Quentien, Jean-Louis Dufier, Centre de recherche en neurobiologie - neurophysiologie de Marseille (CRN2M), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche thérapeutique en ophtalmologie, Université Paris Descartes - Paris 5 (UPD5)-EA2502, EA no 2502 du ministère de la Recherche, de l'Enseignement Supérieur et la Technologie, Université Paris Descartes - Paris 5 (UPD5)-CERTO, Service d'ophtalmologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Centre d'étude et de recherche thérapeutiques en ophtalmologie, Université Paris Descartes - Paris 5 (UPD5), Aix Marseille Université (AMU) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5) - EA2502, Université Paris Descartes - Paris 5 (UPD5) - CERTO, Assistance publique - Hôpitaux de Paris (AP-HP) - CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
MESH : Cell Line, MESH : Transcription Factors, MESH : Transcription Factor Pit-1, Mutant, Electrophoretic Mobility Shift Assay, MESH : Blotting, Western, MESH : Promoter Regions, Genetic, medicine.disease_cause, MESH : Pituitary Gland, 0302 clinical medicine, Endocrinology, MESH : Prolactin, MESH: Pituitary Gland, MESH: Human Growth Hormone, MESH: Animals, MESH : Transcriptional Activation, MESH : Homeodomain Proteins, Eye Abnormalities, Promoter Regions, Genetic, 0303 health sciences, Mutation, MESH: Anterior Eye Segment, Human Growth Hormone, Eye Diseases, Hereditary, MESH: Transcription Factors, Transfection, MESH: Eye Abnormalities, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], Cell biology, MESH : Electrophoretic Mobility Shift Assay, Pituitary Gland, MESH : Mutation, Transcription Factor Pit-1, hormones, hormone substitutes, and hormone antagonists, Transcriptional Activation, congenital, hereditary, and neonatal diseases and abnormalities, medicine.medical_specialty, MESH: Mutation, Blotting, Western, MESH: Prolactin, Biology, MESH : Anterior Eye Segment, Cell Line, [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], 03 medical and health sciences, stomatognathic system, Anterior Eye Segment, Internal medicine, MESH : Eye Abnormalities, MESH: Promoter Regions, Genetic, MESH: Homeodomain Proteins, medicine, MESH: Blotting, Western, Animals, Humans, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], MESH : Human Growth Hormone, Molecular Biology, Transcription factor, Gene, 030304 developmental biology, Homeodomain Proteins, Reporter gene, MESH: Humans, POU domain, MESH : Humans, Promoter, MESH: Cell Line, Prolactin, stomatognathic diseases, MESH: Electrophoretic Mobility Shift Assay, 030221 ophthalmology & optometry, MESH: Transcriptional Activation, MESH : Animals, sense organs, MESH: Transcription Factor Pit-1, Transcription Factors
Abstract

International audience; The bicoid-like transcription factor PITX2 has been previously described to interact with the pituitary-specific POU homeodomain factor POU1F1 (human ortholog of PIT-1) to achieve cell-specific expression of prolactin (PRL) and GH in pituitary somatolactotroph cells. In this work, we have investigated the functional properties of three PITX2 mutants reported in Axenfeld-Rieger syndrome patients relative to the regulation of these genes, using reporter genes under the control of human PRL (hPRL), hGH, or POU1F1 promoters transfected in nonpituitary and pituitary cell lines. Among the three mutations studied, Y167X and E101X introduce a premature stop codon, and F104L leads to an amino acid substitution. While PITX2(E101X) is not expressed in the cells following transfection, and PITX2(F104L) is functionally inactive, the PITX2(Y167X) mutant keeps its DNA-binding capacity and displays a markedly enhanced activation of the hPRL and POU1F1 promoters, but not of the hGH promoter. Y167X is the first mutation of PITX2 described to result in a differential effect on the activation of its different physiological targets, hPRL and POU1F1 on one hand and hGH on the other hand. The differential effect of the Y167X mutation might be linked to an interaction of PITX2 with different transcription factors or cofactors when bound to the hPRL and POU1F1 or the hGH promoters. These results might form the basis for the identification of the PITX2 protein complex necessary for the differential GH or PRL expression.

Published
2010
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4. Description of the SAGhE Cohort: A Large European Study of Mortality and Cancer Incidence Risks after Childhood Treatment with Recombinant Growth Hormone

Author

Swerdlow , Anthony, Cooke , Rosie, Albertsson-Wikland , Kerstin, Borgström , Birgit, Butler , Gary, Cianfarani , Stefano, Clayton , Peter, Coste , Joël, Deodati , Annalisa, Ecosse , Emmanuel, Gausche , Ruth, Giacomozzi , Claudio, Kiess , Wieland, Hokken-Koelega , Anita, Kuehni , Claudia, Landier , Fabienne, Maes , Marc, Mullis , Primus-E, Pfaffle , Roland, Sävendahl , Lars, Sommer , Grit, Thomas , Muriel, Tollerfield , Sally, Zandwijken , Gladys, Carel , Jean-Claude, UCL - SSS/IREC/PEDI - Pôle de Pédiatrie, UCL - (SLuc) Unité d'endocrinologie pédiatrique, Institute of Cancer Research - ICR [London, U.K.], Sahlgrenska Academy at University of Gothenburg [Göteborg], Karolinska Institutet [Stockholm], Institute of Child Health [London], University College of London [London] (UCL), University College London Hospitals (UCLH), IRCCS Ospedale Pediatrico Bambino Gesù [Roma], Royal Manchester Children's Hospital, University of Manchester [Manchester], Unité d’Epidémiologie et de Biostatistiques [APHP Cochin-Broca-Hôtel Dieu], AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université Paris Descartes - Paris 5 (UPD5)-Université de Lorraine (UL), Universität Leipzig [Leipzig], Erasmus University Medical Center [Rotterdam] (Erasmus MC), Sophia Children's Hospital, Institute of Social and Preventive Medicine [Bern] (ISPM), Universität Bern [Bern], Centre de Référence des Maladies Endocriniennes Rares de la Croissance [APHP Robert Debré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Service d'endocrinologie diabétologie pédiatrique [CHU Debré], AP-HP Hôpital universitaire Robert-Debré [Paris], Université Paris Diderot - Paris 7 (UPD7), Centre d'Investigation Clinique - Epidemiologie Clinique/essais Cliniques Hopital Robert Debre, Institut National de la Santé et de la Recherche Médicale (INSERM), Cliniques universitaires St Luc [Bruxelles], Inselspital Bern, Belgian Study Group for Pediatric Endocrinology (BSGPE), Universitair Ziekenhuis Brussel, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), University College of London [London] ( UCL ), University College London Hospitals ( UCLH ), Maladies chroniques, santé perçue, et processus d'adaptation. Approches épidémiologiques et psychologiques. ( APEMAC - EA 4360 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Université de Lorraine ( UL ), Erasmus Medical Center / Dutch Growth Research Foundation, Erasmus University Medical Center [Rotterdam], Institute of Social and Preventive Medicine [Bern] ( ISPM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 ( UPD7 ), Université Paris Diderot - Paris 7 ( UPD7 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ), Belgian Study Group for Pediatric Endocrinology ( BSGPE ), and Pediatrics

Subjects
Male, MESH : Risk, MESH : Child, Preschool, Cohort Studies, MESH: Cause of Death, MESH: Recombinant Proteins, MESH : Child, Cause of Death, Neoplasms, MESH: Child, MESH: Human Growth Hormone, MESH : Female, MESH: Neoplasms, MESH: Incidence, Child, MESH: Cohort Studies, Growth Disorders, Cancer, MESH: Risk, Human Growth Hormone, Incidence, MESH: Infant, Newborn, Cohort, MESH : Infant, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Follow-Up Studies, MESH: Growth Disorders, MESH: Infant, MESH : Incidence, Recombinant Proteins, Europe, MESH: Young Adult, Child, Preschool, Female, Risk, Adolescent, MESH : Recombinant Proteins, MESH : Male, MESH : Europe, MESH : Young Adult, MESH : Cohort Studies, 610 Medicine & health, MESH : Infant, Newborn, Young Adult, SDG 3 - Good Health and Well-being, 360 Social problems & social services, MESH : Adolescent, Humans, MESH : Growth Disorders, MESH : Human Growth Hormone, Mortality, Growth hormone, MESH : Cause of Death, Settore MED/38 - Pediatria Generale e Specialistica, MESH: Adolescent, Original Paper, MESH: Humans, MESH : Humans, MESH: Child, Preschool, Infant, Newborn, Infant, MESH : Follow-Up Studies, MESH : Neoplasms, MESH: Male, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Europe, MESH: Female, Follow-Up Studies
Abstract

International audience; BACKGROUND:The long-term safety of growth hormone treatment is uncertain. Raised risks of death and certain cancers have been reported inconsistently, based on limited data or short-term follow-up by pharmaceutical companies.PATIENTS AND METHODS:The SAGhE (Safety and Appropriateness of Growth Hormone Treatments in Europe) study assembled cohorts of patients treated in childhood with recombinant human growth hormone (r-hGH) in 8 European countries since the first use of this treatment in 1984 and followed them for cause-specific mortality and cancer incidence. Expected rates were obtained from national and local general population data. The cohort consisted of 24,232 patients, most commonly treated for isolated growth failure (53%), Turner syndrome (13%) and growth hormone deficiency linked to neoplasia (12%). This paper describes in detail the study design, methods and data collection and discusses the strengths, biases and weaknesses consequent on this.CONCLUSION:The SAGhE cohort is the largest and longest follow-up cohort study of growth hormone-treated patients with follow-up and analysis independent of industry. It forms a major resource for investigating cancer and mortality risks in r-hGH patients. The interpretation of SAGhE results, however, will need to take account of the methods of cohort assembly and follow-up in each country.

Published
2015
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5. A monocentric experience of growth hormone replacement therapy in adult patients

Author

Lyès Abdi, Frederic Castinetti, Thierry Brue, Frédérique Albarel, Roch Giorgi, Isabelle Morange, M Sahnoun-Fathallah, Service d'endocrinologie, diabète et maladies métaboliques, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre de recherche en neurobiologie - neurophysiologie de Marseille (CRN2M), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U912 INSERM - Aix Marseille Univ - IRD), Institut de Recherche pour le Développement (IRD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Dumonceaud, Corinne, and Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, Endocrinology, Diabetes and Metabolism, Growth hormone, 0302 clinical medicine, Endocrinology, Quality of life, Bone Density, Surveys and Questionnaires, MESH: Human Growth Hormone, [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], MESH: Bone Density, Bone mineral, MESH: Aged, MESH: Middle Aged, Human Growth Hormone, MESH: Hormone Replacement Therapy, General Medicine, Middle Aged, MESH: Patient Compliance, 3. Good health, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Body Composition, Female, France, Adult, medicine.medical_specialty, Waist, Hormone Replacement Therapy, 030209 endocrinology & metabolism, Growth hormone deficiency, 03 medical and health sciences, Internal medicine, medicine, Humans, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Aged, Retrospective Studies, Femoral neck, MESH: Humans, Adult patients, business.industry, MESH: Questionnaires, MESH: Quality of Life, Retrospective cohort study, MESH: Adult, MESH: Retrospective Studies, MESH: Body Composition, medicine.disease, MESH: Male, Surgery, MESH: France, Quality of Life, Patient Compliance, business, MESH: Female
Abstract

International audience; To describe the results of growth hormone (GH) therapy in adult GH-deficient patients treated in a tertiary referral center, with a focus on quality of life and adherence. Retrospective study of patients followed over a total period of 11 years. Quality of life (QOL) was assessed by the QOL-Assessment of Growth Hormone Deficiency in Adults (QoL-AGHDA) score and adherence to treatment was measured by a specific questionnaire. Clinical, biological, body composition and bone mineralization parameters were also analyzed. Data from 81 patients were analyzed. After a median treatment duration of 7 years, 2/3 of patients reported improved QOL (mean decrease of AGHDA score of 3.0 points, P

Published
2014

6. Characterization of the human acth receptor gene andin vitroexpression

Author

C. Jaillard, Danielle Naville, Philippe Durand, J.M. Saez, Stéphane Fontanay, Armelle Penhoat, L. Barjhoux, Martine Begeot, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Communications cellulaires et différenciation, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Hôpital Debrousse, Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biologie des Interactions Neurones / Glie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Microbiologie, adaptation et pathogénie (MAP), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), INRA - SAS (INRA SAS), Institut National de la Recherche Agronomique (INRA), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sol Agro et hydrosystème Spatialisation (SAS), Institut National de la Recherche Agronomique (INRA)-AGROCAMPUS OUEST, Communications Cellulaires et Différenciation (CCD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), and ProdInra, Migration

Subjects
[SDV.BIO]Life Sciences [q-bio]/Biotechnology, Polyadenylation, [SDV]Life Sciences [q-bio], Melanoma, Experimental, Gene Expression, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], [SDV.BID.SPT]Life Sciences [q-bio]/Biodiversity/Systematics, Phylogenetics and taxonomy, Exon, 0302 clinical medicine, Endocrinology, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Cyclic AMP, Tumor Cells, Cultured, MESH: Human Growth Hormone, Coding region, Promoter Regions, Genetic, Receptor, Cells, Cultured, ComputingMilieux_MISCELLANEOUS, MESH: Cyclic AMP, 0303 health sciences, 030219 obstetrics & reproductive medicine, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Human Growth Hormone, EXPRESSION DU GENE, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], MESH: DNA, Exons, General Medicine, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], [SDV] Life Sciences [q-bio], MESH: Melanoma, Experimental, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], MESH: Cells, Cultured, MESH: Gene Expression, Biology, Transfection, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, 03 medical and health sciences, Adrenocorticotropic Hormone, [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication, MESH: Promoter Regions, Genetic, Humans, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, ACTH receptor, MESH: Tumor Cells, Cultured, Northern blot, MESH: Adrenocorticotropic Hormone, Gene, 030304 developmental biology, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, SURRENALE, MESH: Humans, [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], MESH: Transfection, Intron, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, DNA, [SDE.ES]Environmental Sciences/Environmental and Society, Molecular biology, [SDV.SP.PG]Life Sciences [q-bio]/Pharmaceutical sciences/Galenic pharmacology, Receptors, Corticotropin, MESH: Receptors, Corticotropin, Adrenal Cortex, MESH: Adrenal Cortex, MESH: Exons, [SDV.EE.IEO]Life Sciences [q-bio]/Ecology, environment/Symbiosis
Abstract

International audience; The coding sequence of the human ACTH receptor, cloned in 1992, contains no intron, but the presence of one intron (of about 18 kb) separating the coding exon from an upstream exon has been demonstrated. One major transcription start site was located in this first exon. Northern blot analysis of cultured human adrenocortical cells revealed several transcripts that can be partly explained by the use of different polyadenylation sites. We have isolated a 1 kb fragment of genomic DNA upstream of exon 1 and studied its basal promoter activity. The sequence of this region shows several putative CREs that could be responsible for the stimulation by ACTH of its own receptors as demonstrated on human adrenocortical cells. To functionally characterize the human ACTH receptor, we have prepared cells stably transfected with either the normal receptor or a mutant receptor. This model allows the study of both binding to ACTH and coupling to adenylate cyclase. Two naturally mutated receptors, described in patients with Familial Glucocorticoid Deficiency, have been studied. Both mutations (C251F and D107N) strongly impaired the binding of ACTH to its receptors and are then responsible for the absence of biological response to ACTH.

Published
1996
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7. Pharmacokinetic similarity of biologics: analysis using nonlinear mixed-effects modeling

Author

F Mentré, A Dubois, Sandro Gsteiger, S Balser, Jean-Louis Steimer, Goonaseelan Pillai, Etienne Pigeolet, Comets, Emmanuelle, Modèles et méthodes de l'évaluation thérapeutique des maladies chroniques (U738 / UMR_S738), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Modeling and Simulation Department, Novartis Pharma AG, Sandoz Biopharmaceutical Development (Sandoz), Sandoz Biopharmaceutical Development, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)

Subjects
MESH: Clinical Trials as Topic, Wald test, 030226 pharmacology & pharmacy, 01 natural sciences, Article, Data modeling, MESH: Recombinant Proteins, 010104 statistics & probability, 03 medical and health sciences, 0302 clinical medicine, Similarity (network science), Pharmacokinetics, Similarity analysis, Econometrics, MESH: Human Growth Hormone, Humans, Medicine, Pharmacology (medical), biologics, MESH: Erythropoietin, 0101 mathematics, Nonlinear mixed effects model, Erythropoietin, Equivalence (measure theory), [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM], Pharmacology, Biological Products, Clinical Trials as Topic, bioequivalence, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], MESH: Humans, Human Growth Hormone, business.industry, MESH: Biological Agents, Crossover study, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Recombinant Proteins, Epoetin Alfa, MESH: Nonlinear Dynamics, Nonlinear Dynamics, nonlinear mixed effects model, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], business, Biological system, non-compartmental analysis, pharmacokinetics
Abstract

International audience; Our objective was to show, using two examples, that a pharmacokinetic (PK) similarity analysis can be performed using nonlinear mixed-effects models (NLMEM). We used two studies that compared different biosimilars: a three-way crossover trial with somatropin and a parallel-group trial with epoetin-α. For both data sets, the results of NLMEM-based analysis were compared with those of noncompartmental analysis (NCA). For the latter analysis, we performed an NLMEM-based equivalence Wald test on secondary parameters of the model: the area under the curve and the maximal concentration. Somatropin PK was described by a one-compartment model and epoetin-α PK by a two-compartment model with linear and Michaelis-Menten elimination. For both studies, similarity of PK was demonstrated by means of both NCA and NLMEM, and both methods led to similar results. Therefore, for establishing similarity, PK data can be analyzed by either of the methods. NCA is an easier approach because it does not require data modeling; however, NLMEM leads to a better understanding of the underlying biological system.

Published
2012
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8. Autocrine proliferative effects of hGH are maintained in primary cultures of human mammary carcinoma cells

Author

Jean Chiesa, Cécile M. Vouyovitch, Samia Gonzalez, Zhengsheng Wu, Pierre Mares, Hichem C. Mertani, Jean-Jacques Diaz, Gérard Morel, Peter E. Lobie, Tao Zhu, Catherine Ferrer, Cécile Arnould, Laboratoire de Cytogénétique, Centre Hospitalier Régional Universitaire de Nîmes ( CHRU Nîmes ), Equipe 8, Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre de génétique et de physiologie moléculaire et cellulaire ( CGPhiMC ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ) -Centre National de la Recherche Scientifique ( CNRS ), Service de gynécologie obstétrique, Hôpital Universitaire Carémeau [Nîmes], Equipe 4, Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), The Liggins Institute and the National Research Centre for Growth and Development, University of Auckland [Auckland], Department of Molecular Medicine and Pathology, Institut de biologie et chimie des protéines [Lyon] ( IBCP ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre de génétique et de physiologie moléculaire et cellulaire (CGPhiMC), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)

Subjects
MESH: Carcinoma, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Cell, MESH : Aged, Stimulation, MESH : Breast Neoplasms, Biochemistry, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, Endocrinology, MESH: Aged, 80 and over, MESH : Tumor Cells, Cultured, Tumor Cells, Cultured, MESH: Human Growth Hormone, MESH : Cell Proliferation, MESH : Female, Receptor, Aged, 80 and over, MESH: Aged, 0303 health sciences, MESH: Middle Aged, Chemistry, Human Growth Hormone, MESH : Carcinoma, Middle Aged, MESH : Adult, 3. Good health, Autocrine Communication, medicine.anatomical_structure, 030220 oncology & carcinogenesis, embryonic structures, Female, MESH: Membrane Proteins, MESH : Autocrine Communication, hormones, hormone substitutes, and hormone antagonists, Adult, medicine.medical_specialty, endocrine system, Context (language use), Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, Internal medicine, MESH: Cell Proliferation, medicine, Humans, MESH : Middle Aged, MESH: Tumor Cells, Cultured, MESH : Human Growth Hormone, Autocrine signalling, MESH : Aged, 80 and over, 030304 developmental biology, Aged, Cell Proliferation, MESH: Humans, Biochemistry (medical), Carcinoma, MESH : Humans, Antagonist, Membrane Proteins, MESH: Adult, Epithelium, In vitro, MESH : Membrane Proteins, MESH: Autocrine Communication, MESH: Female, MESH: Breast Neoplasms
Abstract

International audience; CONTEXT: Empirical evidence suggests that autocrine human GH (hGH) may possess a proliferative and oncogenic role in human mammary carcinoma. However, this concept is largely derived from studies using cultured human mammary carcinoma cell (HMCC) lines. OBJECTIVE: We investigated the expression and functionality of hGH and the hGH receptor in isolated cultures of primary HMCC. Design: Epithelial cell adhesion molecule-positive primary HMCC were isolated from surgical biopsies of patients with mammary carcinoma and cultured in vitro. Expression of hGH and hGH receptor was determined by RT-PCR, immunofluorescence microscopy, and ELISA. The proliferative response of the cultured primary HMCC to hGH stimulation or hGH inhibition with a hGH antagonist was determined. RESULTS: One hundred percent of cultured primary HMCC expressed the hGH receptor, and 52% expressed hGH at the mRNA level. hGH-positive primary HMCC produced hGH protein within the cell and secreted hGH to the media. Both hGH-negative and hGH-positive HMCC responded to hGH stimulation with large increases in cell number. hGH-positive HMCC responded to inhibition of hGH by a hGH antagonist with a decrease in cell number, whereas hGH-negative HMCC did not. CONCLUSION: Primary HMCC proliferate in response to hGH, and the proliferation of hGH-positive HMCC is inhibited by hGH antagonism. Inhibition of hGH in patients with mammary carcinoma may therefore limit tumor growth.

Published
2011
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9. Growth hormone potentiates thyroid hormone effects on post-exercise phosphocreatine recovery in skeletal muscle

Author

E. Jeannesson, Pierre Kaminsky, F Barbé, Joelle Deibener, Marc Klein, Jean Marie Escanyé, Paul Walker, Brigitte Dousset, Service de médecine interne, Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Laboratoire Electronique, Informatique et Image ( Le2i ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), Pôle des Spécialités Médicales, Laboratoire de Biochimie des Protéines, Service de Médecine Nucléaire [Nancy], laboratoire de methodologie RMN, Université Henri Poincaré - Nancy 1 ( UHP ) -Centre National de la Recherche Scientifique ( CNRS ), Service de Biochimie et Biologie Moléculaire, Nutrition et Métabolisme [CHRU Nancy], Service d'Endocrinologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Laboratoire Electronique, Informatique et Image [UMR6306] (Le2i), Université de Bourgogne (UB)-École Nationale Supérieure d'Arts et Métiers (ENSAM), Arts et Métiers Sciences et Technologies, HESAM Université (HESAM)-HESAM Université (HESAM)-Arts et Métiers Sciences et Technologies, HESAM Université (HESAM)-HESAM Université (HESAM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), and Université Henri Poincaré - Nancy 1 (UHP)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, Phosphocreatine, Thyroid hormones, Endocrinology, Diabetes and Metabolism, MESH: Random Allocation, Thyroid Gland, Skeletal muscle, Hypopituitarism, MESH: Physical Conditioning, Animal, MESH: Drug Synergism, Nuclear magnetic resonance, chemistry.chemical_compound, Random Allocation, 0302 clinical medicine, Endocrinology, MESH: Human Growth Hormone, MESH: Animals, MESH : Muscle, Skeletal, 0303 health sciences, MESH: Muscle, Skeletal, [ INFO.INFO-IM ] Computer Science [cs]/Medical Imaging, MESH : Rats, Human Growth Hormone, Thyroid, Drug Synergism, medicine.anatomical_structure, medicine.drug, medicine.medical_specialty, MESH : Drug Synergism, MESH: Rats, MESH : Male, Somatotropin, 030209 endocrinology & metabolism, MESH: Phosphocreatine, MESH : Random Allocation, 03 medical and health sciences, In vivo, Internal medicine, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, Physical Conditioning, Animal, MESH : Thyroxine, medicine, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Animals, Humans, MESH : Phosphocreatine, MESH : Human Growth Hormone, Mitochondrion, MESH : Physical Conditioning, Animal, Muscle, Skeletal, 030304 developmental biology, Hydrocortisone, MESH: Humans, MESH : Humans, MESH : Thyroid Gland, MESH: Thyroxine, medicine.disease, MESH: Male, MESH: Thyroid Gland, Rats, Thyroxine, chemistry, Rat, MESH : Animals, Tetanic stimulation, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Hormone
Abstract

International audience; OBJECTIVE: The aim of the study was to determine the respective impact of thyroxine and growth hormone on in vivo skeletal mitochondrial function assessed via post exercise phosphocreatine recovery. DESIGN: The hind leg muscles of 32 hypophysectomized rats were investigated using (31)P nuclear magnetic resonance spectroscopy at rest and during the recovery period following a non tetanic stimulation of the sciatic nerve. Each rat was supplemented with hydrocortisone and was randomly assigned to one of the 4 groups: the group Hx was maintained in hypopituitarism., the group HxT was treated with 1 μg/100g/day of thyroxine (T4), the group HxG with 0.2 IU/kg/day of recombinant human GH (rGH) and the group HxGT by both thyroxine and rGH. Inorganic phosphate (Pi), phosphocreatine (PCr) and ATP were directly measured on the spectra, permitting the calculation of the phosphorylation potential (PP). RESULTS: At rest, the rats treated with rGH or T4 exhibited higher PCr levels than rats Hx. The recovery rates of PCr and PP were higher in rats treated with T4 than in T4-deprivated rats, suggesting improved mitochondrial function. The rats treated by both T4 and rGH showed higher PCr and PP recovery than those maintained in hypopituitarism or treated with T4 or rGH alone. CONCLUSIONS: The study demonstrates that in contrast to T4, GH given alone in hypophysectomized rats does not improve in vivo mitochondrial oxidative metabolism. Growth hormone potentiates T4 effects on oxidative metabolism.

Published
2011
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10. Diabetes in acromegaly, prevalence, risk factors, and evolution: data from the French Acromegaly Registry

Author

Sandrine Fieffe, Isabelle Morange, Patrick Petrossians, Philippe Chanson, Vincent Rohmer, Christine Cortet, Françoise Borson-Chazot, Thierry Brue, Brigitte Delemer, Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), CHU de Liège (Endocrinologie), service d'endocrinologie, Récepteurs stéroïdiens : physiopathologie endocrinienne et métabolique, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR93-Université Paris-Sud - Paris 11 (UP11), E04, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche en neurobiologie - neurophysiologie de Marseille (CRN2M), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Endocrinologie - Diabète - Nutrition [Reims], Université de Reims Champagne-Ardenne (URCA)-Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Université Paris-Sud - Paris 11 (UP11)-IFR93-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, Databases, Factual, MESH: Registries, Endocrinology, Diabetes and Metabolism, MESH: Insulin-Like Growth Factor I, Disease, 030204 cardiovascular system & hematology, MESH: Hypertension, Body Mass Index, MESH: Magnetic Resonance Imaging, 0302 clinical medicine, Endocrinology, MESH: Aged, 80 and over, Risk Factors, MESH: Risk Factors, MESH: Child, Epidemiology, MESH: Human Growth Hormone, Registries, Insulin-Like Growth Factor I, Young adult, Child, Aged, 80 and over, 2. Zero hunger, MESH: Aged, education.field_of_study, MESH: Middle Aged, Human Growth Hormone, General Medicine, MESH: Follow-Up Studies, Middle Aged, Magnetic Resonance Imaging, 3. Good health, MESH: Diabetes Complications, MESH: Young Adult, Hypertension, Disease Progression, Female, MESH: Disease Progression, France, Adult, medicine.medical_specialty, Adolescent, Population, 030209 endocrinology & metabolism, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH: Multivariate Analysis, MESH: Body Mass Index, Diabetes Complications, MESH: Sex Ratio, Young Adult, 03 medical and health sciences, Internal medicine, Diabetes mellitus, Acromegaly, medicine, Humans, Pituitary Neoplasms, Sex Ratio, Risk factor, MESH: Pituitary Neoplasms, education, Aged, MESH: Adolescent, MESH: Humans, business.industry, MESH: Biological Markers, MESH: Adult, medicine.disease, MESH: Databases, Factual, MESH: Male, MESH: France, Multivariate Analysis, business, Body mass index, MESH: Acromegaly, MESH: Female, Biomarkers, Follow-Up Studies
Abstract

ObjectivesThe French Acromegaly Registry records data of acromegalic patients' since 1992 in French, Belgian (Liège), and Swiss (Lausanne) centers. We studied the prevalence of diabetes in this population looking for risk factors. Patients from one of the centers (Reims) were then analyzed more thoroughly.MethodsThis study has been conducted on all the patients recorded from 1999 until 2004 (519 patients). Evolution of cohorts' was reassessed in 2009. Of the different variables recorded in the registry: age, sex, body mass index (BMI), duration of acromegaly, GH, IGF1 and prolactin levels, pituitary tumor size, hormonal deficiencies, presence, duration and treatment of diabetes, hypertension, and rheumatological disease were analyzed.ResultsThe prevalence of diabetes in the registry was 22.3%. Diabetic patients were older and had a higher BMI. Compared with the data of the French Social Security, acromegalic patients showed a more precocious apparition of diabetes and prevalence was higher in each age group.Compared with non-diabetic acromegalic subjects, diabetic patients had a more prolonged evolution of acromegaly before diagnosis. The levels of GH and IGF1 were not significantly different between the two groups. Only hypertension was significantly more frequent in diabetic patients.ConclusionsIn our population, the prevalence of diabetes was estimated to be 22.3%. The GH and IGF1 levels did not appear as predictive factors for the presence of diabetes. On the contrary, age, BMI, and hypertension were significant risk factors as in the general population of type 2 diabetics.

Published
2011
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11. Molecular mechanisms of pituitary organogenesis: In search of novel regulatory genes

Author

Shannon W. Davis, Berenice B. Mendonca, Robert H. Lyons, Buffy S. Ellsworth, Sally A. Camper, Frederic Castinetti, Piero Carninci, Mary Anne Potok, Lori T. Raetzman, Luciani R. Carvalho, Amanda H. Mortensen, Ivo J.P. Arnhold, Yoshihide Hayashizaki, Thierry Brue, Michelle L. Brinkmeier, University of Michigan Medical School [Ann Arbor], University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Centre de recherche en neurobiologie - neurophysiologie de Marseille (CRN2M), and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, Pituitary gland, Organogenesis, Hypopituitarism, Cell Communication, Fibroblast growth factor, Bioinformatics, Biochemistry, Mice, 0302 clinical medicine, Endocrinology, MESH: Pituitary Gland, MESH: Gene Expression Regulation, Developmental, MESH: Human Growth Hormone, MESH: Animals, Regulator gene, Genetics, 0303 health sciences, Human Growth Hormone, Wnt signaling pathway, Gene Expression Regulation, Developmental, MESH: Transcription Factors, 3. Good health, medicine.anatomical_structure, Pituitary Gland, Female, MESH: Genes, Developmental, endocrine system, Biology, Article, 03 medical and health sciences, MESH: Cell Communication, MESH: Homeodomain Proteins, medicine, Animals, Humans, Genes, Developmental, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Molecular Biology, Transcription factor, MESH: Mice, 030304 developmental biology, Homeodomain Proteins, MESH: Humans, medicine.disease, MESH: Male, MESH: Organogenesis, T-box, NEUROD1, MESH: Female, 030217 neurology & neurosurgery, Transcription Factors
Abstract

International audience; Defects in pituitary gland organogenesis are sometimes associated with congenital anomalies that affect head development. Lesions in transcription factors and signaling pathways explain some of these developmental syndromes. Basic research studies, including the characterization of genetically engineered mice, provide a mechanistic framework for understanding how mutations create the clinical characteristics observed in patients. Defects in BMP, WNT, Notch, and FGF signaling pathways affect induction and growth of the pituitary primordium and other organ systems partly by altering the balance between signaling pathways. The PITX and LHX transcription factor families influence pituitary and head development and are clinically relevant. A few later-acting transcription factors have pituitary-specific effects, including PROP1, POU1F1 (PIT1), and TPIT (TBX19), while others, such as NeuroD1 and NR5A1 (SF1), are syndromic, influencing development of other endocrine organs. We conducted a survey of genes transcribed in developing mouse pituitary to find candidates for cases of pituitary hormone deficiency of unknown etiology. We identified numerous transcription factors that are members of gene families with roles in syndromic or non-syndromic pituitary hormone deficiency. This collection is a rich source for future basic and clinical studies.

Published
2009
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12. Bone mineral density of young boy soccer players at different pubertal stages: relationships with hormonal concentration

Author

Zouhair Tabka, Ammar Nebigh, Christian Alexandre, Afef Bahlous, Haithem Rebai, Slahedine Sellami, Mohamed Elloumi, Monia Zaouali, Mohamed Zouch, Laboratoire de Physiologie et des Explorations Fonctionnelles [Tunisie], Faculté de Médecine Ibn Eljazzar, Laboratoire des Adaptations Métaboliques à l'Exercice en Conditions Physiologiques et Pathologiques (AME2P), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-UFR Sciences et Techniques des Activités Physiques et Sportives - Clermont-Ferrand (UFR STAPS - UBP), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP), Service Rhumatologie, Hôpital La Rabta [Tunis], Contraintes mécaniques et tissu osseux, Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Vico, Laurence, and Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, MESH: Insulin-Like Growth Factor I, MESH: Insulin-Like Growth Factor Binding Proteins, 0302 clinical medicine, Absorptiometry, Photon, Bone Density, MESH: Human Growth Hormone, Medicine, MESH: Puberty, Testosterone, Insulin-Like Growth Factor I, MESH: Bone Density, Bone mineral, Human Growth Hormone, MESH: Bone and Bones, Control subjects, Insulin-Like Growth Factor Binding Proteins, medicine.anatomical_structure, Lumbar spine, Bone mass, musculoskeletal diseases, medicine.medical_specialty, Somatotropic cell, Adolescent, MESH: Testosterone, 030209 endocrinology & metabolism, MESH: Soccer, MESH: Absorptiometry, Photon, Bone and Bones, 03 medical and health sciences, Rheumatology, Internal medicine, MESH: Body Height, Soccer, Humans, Femoral neck, MESH: Adolescent, MESH: Humans, business.industry, Body Weight, Puberty, 030229 sport sciences, Body Height, MESH: Male, MESH: Body Weight, Endocrinology, Insulin-Like Growth Factor Binding Protein 3, business, human activities, Hormone
Abstract

International audience; OBJECTIVES: To examine the effects of soccer in relation with the hormonal concentration, on the bone mass of young Tunisian players at different pubertal stages. METHODS: Two groups of 152 young boys (age: 13.3+/-0.9 years) participated in this study: (1) 91 soccer players, and (2) 61 non-athletic boys used as control subjects. The bone mineral density (BMD) and the bone mineral content (BMC) were measured by dual-energy X-ray absorptiometry (DXA). Pubertal stages were assessed, and serum concentrations of insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3), growth hormone (GH) and the total testosterone were measured. RESULTS: The BMD and BMC for whole body, lumbar spine, femoral neck, pelvis and lower limbs were higher in soccer players than in controls (p

Published
2009
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13. Antitumor effects of somatostatin

Author

Stéphane Pyronnet, Christiane Susini, Souad Najib, Hanane Laklai, Rania Azar, Corinne Bousquet, Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Simon, Marie Francoise

Subjects
MESH: Signal Transduction, Pituitary gland, MESH: Somatostatin, Apoptosis, MESH: Cell Cycle, Biochemistry, 0302 clinical medicine, Endocrinology, Neoplasms, Somatostatin receptor 3, MESH: Human Growth Hormone, Somatostatin receptor 2, Somatostatin receptor 1, MESH: Animals, MESH: Neoplasms, Receptors, Somatostatin, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, Somatostatin receptor, Human Growth Hormone, Cell Cycle, Life Sciences, MESH: Antineoplastic Agents, Hormonal, 3. Good health, medicine.anatomical_structure, Somatostatin, 030220 oncology & carcinogenesis, Pancreas, hormones, hormone substitutes, and hormone antagonists, Signal Transduction, medicine.medical_specialty, endocrine system, Antineoplastic Agents, Hormonal, Biology, 03 medical and health sciences, Internal medicine, MESH: Cell Proliferation, medicine, MESH: Receptors, Somatostatin, Endocrine system, Animals, Humans, Molecular Biology, 030304 developmental biology, Cell Proliferation, MESH: Humans, MESH: Apoptosis, Cancer research
Abstract

International audience; Since its discovery three decades ago as an inhibitor of GH release from the pituitary gland, somatostatin has attracted much attention because of its functional role in the regulation of a wide variety of physiological functions in the brain, pituitary, pancreas, gastrointestinal tract, adrenals, thyroid, kidney and immune system. In addition to its negative role in the control of endocrine and exocrine secretions, somatostatin and analogs also exert inhibitory effects on the proliferation and survival of normal and tumor cells. Over the past 15 years, studies have begun to reveal some of the molecular mechanisms underlying the antitumor activity of somatostatin. This review covers the present knowledge in the antitumor effect of somatostatin and analogs and discusses the perspectives of novel clinical strategies based on somatostatin receptor sst2 gene transfer therapy.

Published
2008
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14. Final height and gonad function after total body irradiation during childhood

Author

Christine Trivin, Jean Michon, Pierre Lemaire, André Baruchel, Helene Esperou, Ana-Claudia Couto-Silva, Raja Brauner, Université Paris Descartes - Paris 5 (UPD5), CHU Necker - Enfants Malades [AP-HP], Service greffe de moelle osseuse, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Conception synthèse et étude d'antitumoraux, Institut Curie-Centre National de la Recherche Scientifique (CNRS), Service d'hématologie pédiatrique, Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), TIMB, Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Institut Curie [Paris]-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Université Paris Descartes - Paris 5 ( UPD5 ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], INSTITUT CURIE-Centre National de la Recherche Scientifique ( CNRS ), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications [Grenoble] ( TIMC-IMAG ), and Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut polytechnique de Grenoble - Grenoble Institute of Technology ( Grenoble INP ) -IMAG-Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut polytechnique de Grenoble - Grenoble Institute of Technology ( Grenoble INP ) -IMAG-Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA )

Subjects
Male, Transplantation Conditioning, MESH : Follicle Stimulating Hormone, Testicle, 0302 clinical medicine, MESH : Child, MESH: Child, Child, 10. No inequality, Growth Disorders, [ INFO.INFO-RO ] Computer Science [cs]/Operations Research [cs.RO], MESH: Transplantation Conditioning, Human Growth Hormone, Hematopoietic Stem Cell Transplantation, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Follow-Up Studies, Total body irradiation, MESH: Growth Disorders, Spermatozoa, MESH : Whole-Body Irradiation, Child, Preschool, Hematologic Neoplasms, 030220 oncology & carcinogenesis, MESH : Hematologic Neoplasms, medicine.medical_specialty, endocrine system, Ovary, Growth hormone deficiency, 03 medical and health sciences, MESH: Sex Factors, MESH : Adolescent, MESH : Hematopoietic Stem Cell Transplantation, MESH: Body Height, MESH : Spermatozoa, Humans, MESH : Ovary, MESH : Testis, MESH: Adolescent, MESH: Age Factors, MESH: Humans, MESH : Humans, MESH: Child, Preschool, MESH : Follow-Up Studies, MESH : Organ Size, MESH: Inhibins, medicine.disease, Endocrinology, Follicle Stimulating Hormone, MESH: Female, Hormone, MESH : Transplantation Conditioning, MESH: Organ Size, MESH : Child, Preschool, Testis, MESH: Follicle Stimulating Hormone, MESH: Human Growth Hormone, MESH : Female, MESH: Radiotherapy Dosage, MESH : Radiotherapy Dosage, MESH: Testis, MESH: Spermatozoa, Age Factors, Radiotherapy Dosage, Organ Size, Hematology, [INFO.INFO-RO]Computer Science [cs]/Operations Research [cs.RO], Growth hormone treatment, medicine.anatomical_structure, Female, medicine.symptom, MESH: Whole-Body Irradiation, Whole-Body Irradiation, MESH: Ovary, Gonad, Adolescent, MESH : Male, MESH : Sex Factors, MESH : Body Height, Short stature, Sex Factors, Internal medicine, medicine, MESH : Growth Disorders, Inhibins, MESH : Human Growth Hormone, MESH: Hematopoietic Stem Cell Transplantation, Transplantation, MESH : Inhibins, business.industry, Body Height, MESH: Male, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH : Age Factors, business, Follow-Up Studies, 030215 immunology, MESH: Hematologic Neoplasms
Abstract

International audience; Short stature and gonad failure can be a side effect of total body irradiation (TBI). The purpose of the study was to evaluate the factors influencing final height and gonad function after TBI. Fifty young adults given TBI during childhood were included. Twenty-seven had been treated with growth hormone (GH). Those given single 10 Grays (Gy) or fractionated 12 Gy TBI had similar characteristics, GH peaks, final heights and gonad function. After the end of GH treatment, 11/20 patients evaluated had GH peak >10 microg/l. Final height was

Published
2006
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