The Effect of Growth Hormone on Growth Hormone Binding
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International Journal of Obesity (2000) 24, Suppl 2, S160±S161 ß 2000 Macmillan Publishers Ltd All rights reserved 0307±0565/00 $15.00 www.nature.com/ijo The]> effect of growth hormone on growth hormone binding protein, leptin and body composition in hypopituitary adults{ CM Florkowski1*, R Barnard2, JH Livesey1, T Veveris3, EA Espiner1 and RA Donald1 1Department of Endocrinology, Christchurch Hospital, Christchurch, New Zealand; 2Co-operative Research Centre for Diagnostic Technologies; and 3Centre for Molecular Biology, Queensland University of Technology, Brisbane, Queensland, Australia International Journal of Obesity (2000) 24, Suppl 2, S160±S161 Keywords: growth hormone; growth hormone binding protein; leptin; hypopituitarism Introduction compared using Pearson product moment correlation coef®cients. Growth hormone binding protein (GHBP) corresponds to the extracellular domain of the GH receptor (GHR) and is closely related to body fat.1,2 The increased fat Results mass and decreased lean muscle mass associated with hypopituitarism in adults can be improved with GH The changes in body fat and leptin in response to GH treatment, and we shown that the reduction in body fat have been reported previously.3 Baseline plasma stores with GH replacement in this group results in a leptin showed a signi®cant correlation with baseline reduction in serum leptin.3 We examined the relation- BMI, r 0.67, P < 0.005 and baseline percentage ship between GHBP, leptin and body composition in total body fat, r 0.81, P < 0.0001.3 There was a GH-de®cient adults, the response of GHBP to GH strong correlation between baseline GHBP and per- replacement in this group and whether baseline GHBP centage total body fat, r 0.83, P < 0.0001, although predicts IGF-I response. there was no signi®cant correlation with baseline body mass index, r 0.41, P 0.08. There was a strong correlation between baseline leptin and GHBP, r 0.88, P < 0.0001. There was no signi®cant corre- Methods lation between baseline IGF-I and GHBP, r 0.049, P 0.84. There was no signi®cant correlation Nineteen adults were studied, mean age 47 y (range between baseline GHBP and change in IGF-I SDS 20 ± 69), with hypopituitarism and GH de®ciency in response to GH replacement, r 0.037. GHBP (mean IGF-I age related SD score of 2.6Æ 0.3) (meanÆ s.e.m.) was signi®cantly (P 0.049) higher and were randomly allocated (in double-blind fashion) on average during the 12 weeks of GH treatment to either GH (up to 0.25 U=kg=week in daily subcu- (1.53Æ 0.25 nM) than on placebo (1.41Æ 0.25 nM) taneous doses) or placebo for 3 months before cross- (Figure 1). over to the opposite treatment arm. GHBP was measured by ligand immunofunctional assay4 (intra- assay CVs 2.9 ± 4.9%), leptin by radioimmunoassay Discussion (Linco Research Inc., St Charles, MO, USA), and body composition, by dual energy X-ray absorptio- We have therefore shown a strong correlation between metry (Lunar, DPX-L, Lunar Radiation Corp Co., GHBP and percentage total body fat, and between Madison, WI, USA). The effect of treatment on GHBP and leptin. We have also shown GHBP levels GHBP was analyzed by two-way analysis of variance to be increased in response to GH replacement in GH- (ANOVA) with repeated measures. Baseline plasma de®cient adults, although that baseline GHBP levels leptin, GHBP and baseline percentage body fat were do not predict IGF-I responses. It could be postulated that GHBP attenuates the action of GH, resulting in increased adiposity and leptin. Alternatively, *Correspondence: Dr CM Florkowski, Department of increased adiposity may promote an increase in Endocrinology, Christchurch Hospital, Christchurch, New GHBP (perhaps mediated by leptin). Our ®ndings Zealand. add support to a role for GHBP in regulation of E-mail: c¯[email protected] {The data in this report is now published in its entirety in Growth body composition, rather than a passive by-product Hormone and IGF Res 1999; 9: 35 ± 40. of increased cellular expression of GH receptors. GHBP, body fat and leptin CM Florkowski et al S161 Figure 1 Analysis of variance with repeated measures for GHBP (meanÆ s.e.m.). A main effect is shown for all growth hormone treated values (closed circles) versus all placebo levels (open circles), irrespective of order of treatment. Overall mean GHBP was higher (P 0.049) during the 12 weeks of GH treatment (1.53Æ 0.28 nM) than during the placebo period (1.41Æ 0.25 nM). 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