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Melissa Bolier Department of Internal Medicine, section Endocrinology, Erasmus Medical Center, Rotterdam, The Netherlands
Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands

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Aart-Jan van der Lelij Department of Internal Medicine, section Endocrinology, Erasmus Medical Center, Rotterdam, The Netherlands

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Geert O Janssens Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands
Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, The Netherlands

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Marry M van den Heuvel-Eibrink Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands
Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands

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Sebastian J C M M Neggers Department of Internal Medicine, section Endocrinology, Erasmus Medical Center, Rotterdam, The Netherlands

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bone mineral density, lean body mass, quality of life, and an increase in fat mass and, possibly, higher incidence of cardiovascular disease ( Molitch et al. 2011 , Tamhane et al. 2018 ). Since 1985, recombinant GHT is used in GHD patients for

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Zvi Laron Endocrinology and Diabetes Research Unit, Schneider Children’s Medical Center, Petah Tikva, Israel

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Haim Werner Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

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The growth hormone–insulin-like growth factor endocrine system The growth hormone (GH)–insulin-like growth factor-1 (IGF-1) endocrine system plays an essential role in the regulation of multiple metabolic and growth processes throughout life

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Yue Wang Liggins Institute, University of Auckland, Auckland, New Zealand
Maurice Wilkins Centre for Molecular Biodiscovery, Auckland, New Zealand

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Stephen M F Jamieson Maurice Wilkins Centre for Molecular Biodiscovery, Auckland, New Zealand
Auckland Cancer Society Research Centre, University of Auckland, Auckland, New Zealand
Department of Pharmacology and Clinical Pharmacology, University of Auckland, Auckland, New Zealand

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Jo K Perry Liggins Institute, University of Auckland, Auckland, New Zealand
Maurice Wilkins Centre for Molecular Biodiscovery, Auckland, New Zealand

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mutation at binding site 2 which abrogates activation of the GHR, as well as eight additional mutations in binding site 1 ( Kopchick et al. 2002 , 2014 , van der Lely & Kopchick 2006 ). Both GH and B2036 have a very short circulating half-life (15

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Jaime Guevara-Aguirre Colegio de Ciencias de la Salud, Universidad San Francisco de Quito, Diego de Robles s/n y Pampite, Cumbayá, Quito, Ecuador
Instituto de Endocrinología IEMYR, Quito, Ecuador
Maastricht University, Maastricht, The Netherlands

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Gabriela Peña Colegio de Ciencias de la Salud, Universidad San Francisco de Quito, Diego de Robles s/n y Pampite, Cumbayá, Quito, Ecuador

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Gabriel Pazmiño Colegio de Ciencias de la Salud, Universidad San Francisco de Quito, Diego de Robles s/n y Pampite, Cumbayá, Quito, Ecuador

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William Acosta Colegio de Ciencias de la Salud, Universidad San Francisco de Quito, Diego de Robles s/n y Pampite, Cumbayá, Quito, Ecuador

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Jannette Saavedra Instituto de Endocrinología IEMYR, Quito, Ecuador

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Daniela Lescano Colegio de Ciencias de la Salud, Universidad San Francisco de Quito, Diego de Robles s/n y Pampite, Cumbayá, Quito, Ecuador

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Alexandra Guevara Instituto de Endocrinología IEMYR, Quito, Ecuador

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Antonio W D Gavilanes Maastricht University, Maastricht, The Netherlands

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physiologic and pathologic conditions help to understand the subtleties of INSR expression and its role in health and disease ( Chettouh et al. 2013 ). While IR-A is mainly present in intrauterine life, adult tissues preferentially express IR-B, and the IR

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Jaime Guevara-Aguirre Colegio de Ciencias de la Salud, Universidad San Francisco de Quito, Diego de Robles s/n y Pampite, Cumbayá, Quito, Ecuador
Instituto de Endocrinología IEMYR, Quito, Ecuador
Maastricht University, Maastricht, The Netherlands

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Gabriela Peña Colegio de Ciencias de la Salud, Universidad San Francisco de Quito, Diego de Robles s/n y Pampite, Cumbayá, Quito, Ecuador

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William Acosta Colegio de Ciencias de la Salud, Universidad San Francisco de Quito, Diego de Robles s/n y Pampite, Cumbayá, Quito, Ecuador

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Gabriel Pazmiño Colegio de Ciencias de la Salud, Universidad San Francisco de Quito, Diego de Robles s/n y Pampite, Cumbayá, Quito, Ecuador

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Jannette Saavedra Instituto de Endocrinología IEMYR, Quito, Ecuador

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Lina Soto Colegio de Ciencias de la Salud, Universidad San Francisco de Quito, Diego de Robles s/n y Pampite, Cumbayá, Quito, Ecuador

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Daniela Lescano Colegio de Ciencias de la Salud, Universidad San Francisco de Quito, Diego de Robles s/n y Pampite, Cumbayá, Quito, Ecuador

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Alexandra Guevara Instituto de Endocrinología IEMYR, Quito, Ecuador

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Antonio W D Gavilanes Maastricht University, Maastricht, The Netherlands

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, distorted and constitutively activated STAT5 signaling has been found in certain cancers ( Gu et al. 2010 ). At the end of this typical ligand autophosphorylation cascade initiated by the IGF-I/IGFIR binding, phosphorylation of docking proteins such as

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Reetobrata Basu Edison Biotechnology Institute, Athens, Ohio, USA

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John J Kopchick Edison Biotechnology Institute, Athens, Ohio, USA
Molecular and Cellular Biology Program, Ohio University, Athens, Ohio, USA
Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio, USA

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that due to the short half-life of GH in circulation (~15 min) a once daily GH sampling often does not elicit the GH status accurately, the implications of the observation are profound. Knowledge of the serum IGF1 status can further clarify if this is

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Vera Chesnokova Pituitary Center, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA

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Shlomo Melmed Pituitary Center, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California, USA

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and non-homologous end-joining, promoting DNA damage accumulation ( Chesnokova et al. 2019 b , 2021 ) and creating a pro-neoplastic environment in aging tissue. These observations may, to some extent, resolve the uncertainty surrounding the role of

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