Document Detail


Early-onset growth hormone deficiency results in diastolic dysfunction in adult-life and is prevented by growth hormone supplementation.
MedLine Citation:
PMID:  21371927     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: The primary goal of growth hormone (GH) replacement is to promote linear growth in children with growth hormone deficiency (GHD). GH and insulin-like growth factor-1 (IGF-1) are also known to have roles in cardiac development and as modulators of myocardial structure and function in the adult heart. However, little is known about cardiac diastolic function in young adults with childhood onset GH deficiency in which GH treatment was discontinued following puberty. The aim of the study was to evaluate the effects of long standing GHD and peri-pubertal or continuous GH replacement therapy on diastolic function in the adult dwarf rat.
DESIGN: The dwarf rat, which possesses a mutation in a transcription factor necessary for development of the somatotroph, does not exhibit the normal peri-pubertal rise in GH around day 28 and was used to model childhood or early-onset GHD (EOGHD). In another group of male dwarfs, GH replacement therapy was initiated at 4 weeks of age when GH pulsatility normally begins. Ten weeks after initiation of injections, GH-treated dwarf rats were divided into 2 groups; continued treatment with GH for 12 weeks (GH-replete) or treatment with saline for 12 weeks. This latter group models GH supplementation during adolescence with GHD beginning in adulthood (adult-onset GHD; AOGHD). Saline-treated heterozygous (HZ) rats were used as age-matched controls. At 26 weeks of age, cardiac function was assessed using invasive or noninvasive (conventional and tissue Doppler) indices of myocardial contractility and lusitropy.
RESULTS: Systolic function, as determined by echocardiography, was similar among groups. Compared with HZ rats and GH-replete dwarfs, the EOGHD group exhibited significant reductions in myocardial relaxation and increases in left ventricular filling pressure, indicative of moderate diastolic dysfunction. This was further associated with a decrease in the cardiac content of sarcoplasmic reticulum Ca(2+) ATPase (SERCA2), one of the important cardiac calcium regulatory proteins. Dwarfs supplemented with GH during the peri-adolescence stage, but not beyond (AOGHD), exhibited a subtle prolongation in the deceleration time to early filling. In contrast, continual GH replacement preserved diastolic function such that the cardiac phenotype of the GH-replete dwarfs resembled that of their age-matched HZ counterpart.
DISCUSSION: Our data indicate that GHD during adolescence leads to overt diastolic dysfunction in early adulthood and this is prevented by continual GH replacement therapy. Since discontinuation of GH replacement following adolescence only mitigated the lusitropic deficits that were observed in untreated dwarfs, GH treatment into adulthood could be beneficial.
Authors:
L Groban; M Lin; K A Kassik; R L Ingram; W E Sonntag
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-03-02
Journal Detail:
Title:  Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society     Volume:  21     ISSN:  1532-2238     ISO Abbreviation:  Growth Horm. IGF Res.     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-05-02     Completed Date:  2011-08-19     Revised Date:  2014-09-21    
Medline Journal Info:
Nlm Unique ID:  9814320     Medline TA:  Growth Horm IGF Res     Country:  Scotland    
Other Details:
Languages:  eng     Pagination:  81-8     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Growth Hormone Research Society. Published by Elsevier Ltd. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Animals
Diastole / physiology
Dwarfism, Pituitary / metabolism
Echocardiography, Doppler
Growth Hormone / administration & dosage*,  deficiency*,  metabolism
Heart / drug effects,  physiopathology*
Humans
Insulin-Like Growth Factor I / metabolism
Male
Rats
Grant Support
ID/Acronym/Agency:
K08 AG026764/AG/NIA NIH HHS; K08 AG026764-05/AG/NIA NIH HHS; K08-AG026764-05/AG/NIA NIH HHS; P01 AG011370/AG/NIA NIH HHS; P01 AG011370/AG/NIA NIH HHS; P01 AG011370-14/AG/NIA NIH HHS; R01 AG026607/AG/NIA NIH HHS; R01 AG026607-06/AG/NIA NIH HHS; R01 AG038747/AG/NIA NIH HHS; R01 AG26607/AG/NIA NIH HHS; R03 AG022598/AG/NIA NIH HHS; R03 AG022598-01/AG/NIA NIH HHS
Chemical
Reg. No./Substance:
67763-96-6/Insulin-Like Growth Factor I; 9002-72-6/Growth Hormone
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