Document Detail


Influence of the d3GH receptor polymorphism on the metabolic and biochemical phenotype of GH-deficient adults at baseline and during short- and long-term recombinant human GH replacement therapy.
MedLine Citation:
PMID:  20592127     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: A common polymorphic variant of GH receptor (exon 3 deletion, d3GHR) has been linked with increased response to recombinant human GH (rhGH) in some patients with or without GH deficiency (GHD). The aim of the study was to investigate the impact of the GHR genotype on the phenotype of GHD adults and on the metabolic effect of rhGH therapy. DESIGN: Prospective study of GHD patients evaluated before and during short- (1 year, n=100) and long-term (5 years, n=50) rhGH therapy. METHODS: Effects of rhGH on IGF1 levels, body composition (body fat percentage, BF%), body mass index, lipid profile, and glucose homeostasis (fasting insulin and glucose, insulin sensitivity indexes) were evaluated according to the presence or the absence of the d3GHR variant. RESULTS: The different genotype did not influence basal phenotype of GHD. Short-term rhGH determined normalization of IGF1 levels, decrease in BF%, and worsening of insulin sensitivity, independently from the presence of the d3GHR allele. A significant increase in high-density lipoprotein cholesterol occurred in the d3GHR group. Normalization of IGF1 levels and decrease in BF% were maintained after 5 years. Insulin sensitivity restored to basal values, though in d3GHR patients fasting glucose remained significantly higher than at baseline. After both 1 and 5 years, percentage of subjects with impaired glucose tolerance, similar in the two groups at baseline, decreased in fl/fl while doubled in d3GHR patients. In this last group, a long-term significant reduction in total and low-density lipoprotein cholesterol was also observed. CONCLUSION: The functional difference of d3GHR may influence some metabolic effects of rhGH on GHD adults.
Authors:
Claudia Giavoli; Emanuele Ferrante; Eriselda Profka; Luca Olgiati; Silvia Bergamaschi; Cristina L Ronchi; Elisa Verrua; Marcello Filopanti; Elena Passeri; Laura Montefusco; Andrea G Lania; Sabrina Corbetta; Maura Arosio; Bruno Ambrosi; Anna Spada; Paolo Beck-Peccoz
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-06-30
Journal Detail:
Title:  European journal of endocrinology / European Federation of Endocrine Societies     Volume:  163     ISSN:  1479-683X     ISO Abbreviation:  Eur. J. Endocrinol.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-08-18     Completed Date:  2010-09-09     Revised Date:  2010-11-15    
Medline Journal Info:
Nlm Unique ID:  9423848     Medline TA:  Eur J Endocrinol     Country:  England    
Other Details:
Languages:  eng     Pagination:  361-8     Citation Subset:  IM    
Affiliation:
Department of Medical Sciences, University of Milan, Milan, Italy. claudiagiavoli@yahoo.it
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MeSH Terms
Descriptor/Qualifier:
Adult
Age Factors
Drug Administration Schedule
Dwarfism, Pituitary / drug therapy,  genetics*,  metabolism
Female
Gene Deletion
Human Growth Hormone / administration & dosage,  deficiency*,  genetics*
Humans
Male
Middle Aged
Phenotype*
Polymorphism, Genetic / genetics*
Prospective Studies
Receptors, Somatotropin / genetics*,  physiology
Time Factors
Chemical
Reg. No./Substance:
0/Receptors, Somatotropin; 12629-01-5/Human Growth Hormone
Comments/Corrections
Comment In:
Nat Rev Endocrinol. 2010 Oct;6(10):535

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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