Growth hormone-binding protein-related immunoreactivity in the serum of patients with acromegaly is regulated inversely by growth hormone concentration

Kratzsch, Jürgen; Blum, Werner; Ventz, Manfred; Selisko, T.; Birkenmeyer, Gerd; Keller, E

doi:10.1530/eje.0.1320306

Cited by 29 publications

(26 citation statements)

References 19 publications

(24 reference statements)

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“…Uric acid was determined with the uricase method (Kodak, Rochester, NY, USA), insulin by a radioimmunoassay (International CIS, Gifsur-Yvette, France) and IGF-I by an ELISA after acid ethanol extraction as described previously. 23 Leptin 24 and GHBP 25 were measured by recently described speci®c in-house' RIAs. Intra-and interassay coef®cients of variation in all immuno-assays were below 9% at half maximum displacement tracer.…”

Section: Methodsmentioning

confidence: 99%

Increased serum GHBP levels in obese pubertal children and adolescents: relationship to body composition, leptin and indicators of metabolic disturbances

et al. 1997

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OBJECTIVE: The serum concentration of the high-af®nity growth hormone-binding protein (GHBP) is increased in obesity but the mechanisms are poorly understood. This study assessed the physiological mechanisms involved in the regulation of GHBP in adiposity. SUBJECTS AND MEASUREMENTS: We tested a number of obesity speci®c parameters for their association with GHBP. In this study, 199 normal or overweight children and adolescents (101 boys, 98 girls, aged (mean AE s.d.): 13.7 AE 2.3 y) underwent an anthropometric evaluation (circumference measurements and bioimpedance analysis) combined with blood withdrawal for the measurement of insulin-like growth factor-I (IGF-I), insulin, leptin and GHBP (by speci®c RIA), uric acid, triglycerides and cholesterol. RESULTS: By linear regression analysis GHBP correlated signi®cantly (P`0.001) with percent body fat mass (r 0X71), waist (r 0X73) and hip (r 0.69) circumference, weight (r 0.61), waist hip ratio (WHR) (r 0.54), as well as with the serum concentrations of leptin (r 0.64), uric acid (r 0.54), insulin (r 0.45), LDL-cholesterol (r 0X43), cholesterol (r 0.33), LDLaHDL ratio (r 0.47), triglycerides (r 0.30) and with height standard deviations scores (SDS) (r 0.23). Age, gender and pubertal stage had no impact on GHBP. In a multiple regression analysis containing age and gender, as well as the anthropometric variables, percent fat mass and waist circumference, as independent variables, associations between GHBP and leptin (P`0.001), cholesterol (P`0.01), LDL-cholesterol (P 0.01), LDLaHDL ratio (P 0.02), triglycerides (P 0.01) remained signi®cant. In a ®nal model using the stepwise analysis involving age, gender and all the independent predictors of GHBP, waist circumference (P`0.001) accounted for 49.5% of the 60.0% total variability in GHBP, while the implication of leptin (P`0.001), age (P`0.01) and cholesterol(P`0.05) increased the predicted variability for 7.5%, 1.9%, and 1.0%, respectively. Serum GHBP was signi®cantly reduced in a subgroup of 104 overweight or obese patients during a diet-induced weight loss programme, the coef®cient of correlation between GHBP and leptin after (r 0.45, P`0.001) and before weight reduction (r 0.41, P 0.001) were comparable. CONCLUSION: Waist circumference, an indicator of abdominal body fat mass, is a major determinant of GHBP levels during childhood, while leptin may be one candidate for a signal linking adipocytes to the growth hormone receptor related GHBP release. Additionally, elevated serum levels of GHBP may re¯ect metabolic disturbances of adiposity.

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Section: Methodsmentioning

confidence: 99%

Increased serum GHBP levels in obese pubertal children and adolescents: relationship to body composition, leptin and indicators of metabolic disturbances

et al. 1997

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“…Recent studies have, however, suggested that the circulating binding protein is also cleaved from a truncated receptor lacking 97.5% of the intracellular part, which is a result of an alternatively spliced mRNA (27,28). High levels of GHBP have been found in conditions with low GH levels, including simple obesity (7,29) and vice versa in, for example, acromegaly and insulin-dependent diabetes mellitus (7,(30)(31)(32)(33). These data suggest that the GH receptor in some way is up-regulated in GH-insufficient conditions.…”

Section: Figurementioning

confidence: 99%

Impact of gender and androgen status on IGF-I levels in normal and GH-deficient adults

Fisker

Jørgensen

Vahl

et al. 1999

European Journal of Endocrinology

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Objective: The regulation of IGF-I levels is complex and not only dependent on GH status, as the diagnostic sensitivity of serum IGF-I levels for GH deficiency (GHD) in adults is low. Other GH-related parameters have so far not proven to be of additional diagnostic value in GHD adults. In the present study we evaluated the impact of gender and androgen status on IGF-I levels and the diagnostic value of IGF-I and GH-related parameters in a population of adult hypopituitary patients and age-and gender-matched healthy subjects. Design: A cross-sectional study.

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“…As GH-binding protein (GHBP) is believed to be derived from proteolytic cleavage of the extracellular domain of the GH receptor and may be regarded as an intrinsic part of the GH-IGF-I axis, an effect of body composition on circulating GHBP levels may be expected (10,11). Some studies have shown that GH and insulin might participate in regulation of GHBP levels (12,13). Little is known, however, about GH secretion and GHBP variations in obesity according to the degree of glucose tolerance.…”

Section: Introductionmentioning

confidence: 99%

GH-binding protein in obese men with varying glucose tolerance: relationship to body fat distribution, insulin secretion and the GH-IGF-I axis

Nam

Kim

Song

et al. 1999

European Journal of Endocrinology

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Bioelectrical impedance for measurement of total body fat and computed tomography for visceral and subcutaneous fat at umbilicus levels were performed in 34 obese and 10 lean men. Insulin secretion in response to an oral glucose tolerance test (OGTT) and a GH stimulation test by L-dopa, growth hormone-binding protein (GHBP) and IGF-I were measured. Obese subjects were divided into three groups according to the OGTT. The obese type II diabetes mellitus group had the highest GHBP levels and the most visceral fat. GHBP levels were most strongly correlated with the ratio of visceral fat area to body weight (VWR) above any other parameters (r = 0.725, P < 0.001). The insulin and free fatty acid (FFA) areas under curves (AUC) during the OGTT, and the IGF-I level, were also positively correlated with GHBP levels (r = 0.474, P < 0.005; r = 0.572, P < 0.005; r = 0.453, P < 0.005). GH-AUC to the L-dopa stimulation test was negatively correlated with GHBP levels (r = ¹0.432, P < 0.005). Stepwise multiple linear regression analysis showed that VWR, FFA-AUC and insulin-AUC significantly contributed to the variability of GHBP (r 2 = 0.58). In conclusion, we demonstrated that: (i) visceral fat amount mainly determined GHBP levels in obese men with varying glucose tolerance; (ii) hyperglycemia per se did not influence the GHBP level, whereas insulin and FFA could play a role in regulation of GHBP; and (iii) although GH was not the main regulator of GHBP, the unchanged IGF-I level despite GH hyposecretion suggests that increased GHBP levels reflect GH hypersensitivity in order to compensate for decreased GH secretion in obesity.

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Growth hormone-binding protein-related immunoreactivity in the serum of patients with acromegaly is regulated inversely by growth hormone concentration

Cited by 29 publications

References 19 publications

Increased serum GHBP levels in obese pubertal children and adolescents: relationship to body composition, leptin and indicators of metabolic disturbances

Increased serum GHBP levels in obese pubertal children and adolescents: relationship to body composition, leptin and indicators of metabolic disturbances

Impact of gender and androgen status on IGF-I levels in normal and GH-deficient adults

GH-binding protein in obese men with varying glucose tolerance: relationship to body fat distribution, insulin secretion and the GH-IGF-I axis

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