Differential effects of GH replacement on the components of the leptin system in GH-deficient individuals.

2.50
Hdl Handle:
http://hdl.handle.net/10541/80139
Title:
Differential effects of GH replacement on the components of the leptin system in GH-deficient individuals.
Authors:
Randeva, Harpal S; Murray, Robert D; Lewandowski, Krzysztof C; O'Callaghan, Chris J; Horn, Rüdiger; O'Hare, Paul; Brabant, Georg E; Hillhouse, Edward W; Shalet, Stephen M
Abstract:
GH therapy is associated with a reduction in fat mass and an increase in lean mass in subjects with GH deficiency (GHD). Leptin, like GH, plays an important role in the regulation of body composition. GH treatment has been shown to reduce serum leptin; however, the physiological interactions between the leptin system (free leptin, bound leptin, and soluble leptin receptor) and the GH/IGF-I system largely remain unknown. Twenty-five patients with childhood (n = 10) and adult-onset (n = 15) GHD were studied. GH status had previously been determined using an insulin tolerance test and/or an arginine stimulation test. The following parameters were recorded at baseline (V1) and then after 3 months (V2) and 6 months (V3) on GH treatment: fat mass, body mass index (BMI), and waist/hip ratio (WHR); blood samples were taken after an overnight fast for free leptin, bound leptin, soluble leptin receptor, insulin, and IGF-I. At V2 and V3, respectively, a fall in free leptin (P < 0.001 for each), and at V3 a fall in in percent fat mass (P < 0.001) were observed. There were no significant changes in BMI or WHR. Simultaneously, there was a rise in insulin (P = 0.068 and P < 0.001), IGF-I (P < 0.001 and P < 0.001), bound leptin (P = 0.005 and P < 0.001), and soluble leptin receptor (P = 0.61 and P < 0.001). A positive relationship was noted between free leptin and BMI (P < 0.001) and between free leptin and fat mass (P < 0.001), and a negative relationship was found between free leptin and IGF-I (P < 0.001) and, within patient, between free leptin and insulin (P < 0.001). There was no significant correlation between free leptin and WHR. Bound leptin had a positive association with IGF-I (P < 0.001) and insulin (P = 0.002) and a negative relationship with percent fat mass (P = 0.023). Soluble leptin receptor was also positively related to IGF-I (P < 0.001). In conclusion, our data suggest that the reduction in serum leptin with GH treatment, as noted by others, is mediated through a fall in free leptin. The fall in free leptin and in part the rise in bound leptin are most likely through a reduction in percent fat mass. However, the observed changes in free leptin and bound leptin and, more importantly, the rise in soluble leptin receptor, are not explained entirely by modifications in body composition and may be a direct result of GH/IGF-I.
Affiliation:
Sir Quinton Hazel Molecular Medicine Research Center, Biological Sciences, University of Warwick, Coventry, United Kingdom CV4 7AL.
Citation:
Differential effects of GH replacement on the components of the leptin system in GH-deficient individuals. 2002, 87 (2):798-804 J. Clin. Endocrinol. Metab.
Journal:
The Journal of Clinical Endocrinology and Metabolism
Issue Date:
Feb-2002
URI:
http://hdl.handle.net/10541/80139
PubMed ID:
11836324
Type:
Article
Language:
en
ISSN:
0021-972X
Appears in Collections:
All Christie Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorRandeva, Harpal S-
dc.contributor.authorMurray, Robert D-
dc.contributor.authorLewandowski, Krzysztof C-
dc.contributor.authorO'Callaghan, Chris J-
dc.contributor.authorHorn, Rüdiger-
dc.contributor.authorO'Hare, Paul-
dc.contributor.authorBrabant, Georg E-
dc.contributor.authorHillhouse, Edward W-
dc.contributor.authorShalet, Stephen M-
dc.date.accessioned2009-09-07T15:34:29Z-
dc.date.available2009-09-07T15:34:29Z-
dc.date.issued2002-02-
dc.identifier.citationDifferential effects of GH replacement on the components of the leptin system in GH-deficient individuals. 2002, 87 (2):798-804 J. Clin. Endocrinol. Metab.en
dc.identifier.issn0021-972X-
dc.identifier.pmid11836324-
dc.identifier.urihttp://hdl.handle.net/10541/80139-
dc.description.abstractGH therapy is associated with a reduction in fat mass and an increase in lean mass in subjects with GH deficiency (GHD). Leptin, like GH, plays an important role in the regulation of body composition. GH treatment has been shown to reduce serum leptin; however, the physiological interactions between the leptin system (free leptin, bound leptin, and soluble leptin receptor) and the GH/IGF-I system largely remain unknown. Twenty-five patients with childhood (n = 10) and adult-onset (n = 15) GHD were studied. GH status had previously been determined using an insulin tolerance test and/or an arginine stimulation test. The following parameters were recorded at baseline (V1) and then after 3 months (V2) and 6 months (V3) on GH treatment: fat mass, body mass index (BMI), and waist/hip ratio (WHR); blood samples were taken after an overnight fast for free leptin, bound leptin, soluble leptin receptor, insulin, and IGF-I. At V2 and V3, respectively, a fall in free leptin (P < 0.001 for each), and at V3 a fall in in percent fat mass (P < 0.001) were observed. There were no significant changes in BMI or WHR. Simultaneously, there was a rise in insulin (P = 0.068 and P < 0.001), IGF-I (P < 0.001 and P < 0.001), bound leptin (P = 0.005 and P < 0.001), and soluble leptin receptor (P = 0.61 and P < 0.001). A positive relationship was noted between free leptin and BMI (P < 0.001) and between free leptin and fat mass (P < 0.001), and a negative relationship was found between free leptin and IGF-I (P < 0.001) and, within patient, between free leptin and insulin (P < 0.001). There was no significant correlation between free leptin and WHR. Bound leptin had a positive association with IGF-I (P < 0.001) and insulin (P = 0.002) and a negative relationship with percent fat mass (P = 0.023). Soluble leptin receptor was also positively related to IGF-I (P < 0.001). In conclusion, our data suggest that the reduction in serum leptin with GH treatment, as noted by others, is mediated through a fall in free leptin. The fall in free leptin and in part the rise in bound leptin are most likely through a reduction in percent fat mass. However, the observed changes in free leptin and bound leptin and, more importantly, the rise in soluble leptin receptor, are not explained entirely by modifications in body composition and may be a direct result of GH/IGF-I.en
dc.language.isoenen
dc.subject.meshAdipose Tissue-
dc.subject.meshAdolescent-
dc.subject.meshAdult-
dc.subject.meshAged-
dc.subject.meshCarrier Proteins-
dc.subject.meshFemale-
dc.subject.meshGrowth Hormone-
dc.subject.meshHumans-
dc.subject.meshInsulin-Like Growth Factor I-
dc.subject.meshLeptin-
dc.subject.meshMale-
dc.subject.meshMiddle Aged-
dc.subject.meshReceptors, Cell Surface-
dc.subject.meshReceptors, Leptin-
dc.titleDifferential effects of GH replacement on the components of the leptin system in GH-deficient individuals.en
dc.typeArticleen
dc.contributor.departmentSir Quinton Hazel Molecular Medicine Research Center, Biological Sciences, University of Warwick, Coventry, United Kingdom CV4 7AL.en
dc.identifier.journalThe Journal of Clinical Endocrinology and Metabolismen
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