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Dual Defects in Pulsatile Growth Hormone Secretion and Clearance Subserve the Hyposomatotropism of Obesity in Man^*

Division of Endocrinology and Metabolism and the Interdisciplinary Graduate Biophysics Program, Departments of Internal Medicine and Pharmacology, University of Virginia (J.D.V., M.L.J.) Charlottesville, Virginia 22908
Salem Veterans Administration Hospital (A.I., G.L.) Salem, Virginia 24153
Garvan Institute of Medical Research, St. Vincent’s Hospital (K.K.Y.H.) Darlinghurst, New South Wales
and the Department of Physiology and Pharmacology, University of Queensland (M.J.W.) Queensland 4067, Australia

Address all correspondence and requests for reprints to: Dr. Johannes D. Veldhuis, Division of Endocrinology and Metabolism, Box 202, Department of Medicine, University of Virginia School of Medicine, Charlottesville, Virginia 22908.

We have examined the mechanisms underlying reduced circulating GH concentrations in the obese human. Computer-assisted (deconvolution) analysis was used to determine endogenous GH secretory and clearance rates quantitatively from entire 24-h plasma GH concentration profiles. These analyses revealed that the half-life (t_1/2) of endogenous GH was significantly shorter in obese (11.7 ± 1.6 min) than in normal weight subjects (15.5 ± 0.81 min; P < 0.01). The accelerated blood disposal rate of GH was not due to decreased circulating concentrations of GH-binding protein, since the latter were similar in obese (25 ± 1.0%) and normal weight (24 ± 2.3%) men. However, obese men had significantly fewer GH secretory bursts (3.2 ± 0.53 vs. 9.7 ± 0.67/day; P < 0.01). Among the rare GH secretory bursts that occurred in obese subjects, there were significantly prolonged mean intersecretory burst intervals (282 ± 65 vs. 131 ± 11 min; P < 0.05). The resultant daily GH production rate in obese men was reduced to one fourth that in normal weight individuals. Both GH secretion rate and burst frequency were negatively correlated with the degree of obesity (ponderal index). The decreases in GH burst frequency and halflife were specific, since GH secretory pulse amplitude (maximal rate of GH release), the mass of GH released per burst, and the duration of computer-resolved GH secretory bursts were not different in obese and normal weight men.

We conclude that obese men harbor a double defect in GH dynamics involving both GH secretion and clearance, and that the severity of the GH secretory deficiency is proportionate to the degree of obesity.

^* This work was supported in part by NIH Grant RR-00847 (to the Clinical Research Center of the University of Virginia), Research Career Development Award 1-KO4-HD-00634 (to J.D.V.), NIH Grant GM-28928 (to M.L.J.), Diabetes and Endocrinology Research Center Grant NIH DK-38942, NIH-supported Clinfo Data Reduction Systems, V.A. Medical Research Funds (to A.I. and G.L.), and support by the Pratt Foundation.

Received May 23, 1990.

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				C. A. M. Roelen, H. P. F. Koppeschaar, W. R. de Vries, Y. E. M. Snel, M. E. Doerga, P. M. J. Zelissen, J. H. H. Thijssen, and M. A. Blankenstein Visceral Adipose Tissue Is Associated with Circulating High Affinity Growth Hormone-Binding Protein J. Clin. Endocrinol. Metab., March 1, 1997; 82(3): 760 - 764. [Abstract] [Full Text] [PDF]

				S. Fisker, N. Vahl, J. O. L. Jorgensen, J. S. Christiansen, and H. Orskov Abdominal Fat Determines Growth Hormone-Binding Protein Levels in Healthy Nonobese Adults J. Clin. Endocrinol. Metab., January 1, 1997; 82(1): 123 - 128. [Abstract] [Full Text] [PDF]