Growth hormone improves growth retardation induced by rapamycin without blocking its antiproliferative and antiangiogenic effects on rat growth plate

Autor: Enrique García-López, Julián Rodríguez-Suárez, Vanessa Loredo, Flor A. Ordoñez, Helena Gil-Peña, Natalia Mejía-Gaviria, Oscar Alvarez-Garcia, Fernando Santos
Rok vydání: 2012
Předmět:
Anatomy and Physiology
Angiogenesis
medicine.medical_treatment
lcsh:Medicine
Gene Expression
Biochemistry
Pediatrics
Muscle hypertrophy
Rats
Sprague-Dawley
Glycogen Synthase Kinase 3
Endocrinology
GSK-3
Growth Retardation
Growth Plate
Insulin-Like Growth Factor I
lcsh:Science
Child
Extracellular Signal-Regulated MAP Kinases
Musculoskeletal System
beta Catenin
Multidisciplinary
Antibiotics
Antineoplastic
Cell Differentiation
medicine.anatomical_structure
Medicine
Female
Chondrogenesis
medicine.drug
Research Article
medicine.medical_specialty
Bone and Mineral Metabolism
Neovascularization
Physiologic
Endocrine System
Biology
Chondrocyte
Chondrocytes
Internal medicine
Growth Factors
medicine
Autophagy
Animals
Humans
Protein kinase B
Sirolimus
Glycogen Synthase Kinase 3 beta
Endocrine Physiology
Growth factor
lcsh:R
Rats
Transplantation
Cartilage
Metabolism
Growth Hormone
lcsh:Q
Zdroj: SCOPUS
RUO. Repositorio Institucional de la Universidad de Oviedo
instname
PLoS ONE
PLoS ONE, Vol 7, Iss 4, p e34788 (2012)
Popis: Rapamycin, an immunosuppressant agent used in renal transplantation with antitumoral properties, has been reported to impair longitudinal growth in young individuals. As growth hormone (GH) can be used to treat growth retardation in transplanted children, we aimed this study to find out the effect of GH therapy in a model of young rat with growth retardation induced by rapamycin administration. Three groups of 4-week-old rats treated with vehicle (C), daily injections of rapamycin alone (RAPA) or in combination with GH (RGH) at pharmacological doses for 1 week were compared. GH treatment caused a 20% increase in both growth velocity and body length in RGH animals when compared with RAPA group. GH treatment did not increase circulating levels of insulin-like growth factor I, a systemic mediator of GH actions. Instead, GH promoted the maturation and hypertrophy of growth plate chondrocytes, an effect likely related to AKT and ERK1/2 mediated inactivation of GSK3β, increase of glycogen deposits and stabilization of β-catenin. Interestingly, GH did not interfere with the antiproliferative and antiangiogenic activities of rapamycin in the growth plate and did not cause changes in chondrocyte autophagy markers. In summary, these findings indicate that GH administration improves longitudinal growth in rapamycin-treated rats by specifically acting on the process of growth plate chondrocyte hypertrophy but not by counteracting the effects of rapamycin on proliferation and angiogenesis.
Databáze: OpenAIRE
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