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Age and Relative Adiposity Are Specific Negative Determinants of the Frequency and Amplitude of Growth Hormone (GH) Secretory Bursts and the Half-Life of Endogenous GH in Healthy Men^*

Endocrine Section, Department of Internal Medicine, Salem Veterans Administration Hospital Salem, Virginia 24153
the Division of Endocrinology and Metabolism, Interdisciplinary Graduate Biophysics Program, Department of Internal Medicine and National Science Foundation Science Center in Biological Timing, University of Virginia Health Sciences Center Charlottesville, Virginia 22908

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

Mean plasma GH concentrations are controlled by the frequency, amplitude, and duration of underlying GH secretory bursts as well as by the half-life of endogenous GH. We investigated the specific mechanisms that subserve the clinically recognized negative effects of age and adiposity on mean serum GH concentrations. To this end, 21 healthy men, aged 21–71 yr, who were of nearly normal body weight underwent blood sampling at 10-min intervals for 24 h. Deconvolution analysis was used to estimate specific features of GH secretion and clearance. Compared to younger men, the older tertile of men had significant reductions in 1) GH secretory burst frequency, 2) the half-life of endogenous GH, and 3) the daily GH secretory rate, but not 4) GH secretory burst half-duration, amplitude, or mass.

Linear regression analysis disclosed that age was a major negative statistical determinant of GH secretory burst frequency (r = –0.80; p = 0.005) and endogenous GH half-life (r = –0.70; p = 0.024). Body mass index, an indicator of relative obesity, was a significant negative correlate of GH half-life (p = 0.045) and GH secretory burst amplitude (p = 0.031). Age and body mass index each correlated negatively with the daily GH secretion rate (p = 0.0031 and p = 0.027, respectively), and together accounted for more than 60% of the variability in 24-h GH production rates (r = –0.78; p = 0.00056). On the average, for a normal body mass index, each decade of increasing age attenuated the GH production rate by 14% and the GH half-life by 6%. Conversely, each unit increase in body mass index, at a given age, reduced the daily GH secretion rate by 6%.

We conclude that age and relative adiposity are distinct and specific correlates of individual attributes of GH secretion and clearance in men.

^* This work was supported in part by NIH Grant RR-00847 (to Clinical Research Center of the University of Virginia), Research Career Development Award 1-KO4-HD-00634 (to J.D.V.), Diabetes and Endocrinology Research Center Grant NIH DK-38942, NIHsupported Clinfo Data Reduction Systems, V.A. Medical Research Funds (to A.I.), Baxter Healthcare Corp., the University of Virginia Pratt Foundation, Education Enhancement Fund, and the NSF Science Center in Biological Timing (to J.D.V.).

Received January 16, 1991.

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				J. C. Lovejoy, S. R. Smith, J. J. Zachwieja, G. A. Bray, M. M. Windhauser, P. J. Wickersham, J. D. Veldhuis, R. Tulley, and J. A. de la Bretonne Low-dose T3 improves the bed rest model of simulated weightlessness in men and women Am J Physiol Endocrinol Metab, August 1, 1999; 277(2): E370 - E379. [Abstract] [Full Text] [PDF]

				P. Vestergaard, A. P. Hermann, H. Ørskov, and L. Mosekilde Effect of Sex Hormone Replacement on the Insulin-Like Growth Factor System and Bone Mineral: A Cross-Sectional and Longitudinal Study in 595 Perimenopausal Women Participating in the Danish Osteoporosis Prevention Study J. Clin. Endocrinol. Metab., July 1, 1999; 84(7): 2286 - 2290. [Abstract] [Full Text]

				M. Zaccaria, M. Varnier, P. Piazza, D. Noventa, and A. Ermolao Blunted Growth Hormone Response to Maximal Exercise in Middle-Aged Versus Young Subjects and No Effect of Endurance Training J. Clin. Endocrinol. Metab., July 1, 1999; 84(7): 2303 - 2307. [Abstract] [Full Text]

				R. K. Støving, J. D. Veldhuis, A. Flyvbjerg, J. Vinten, J. Hangaard, O. G. Koldkjær, J. Kristiansen, and C. Hagen Jointly Amplified Basal and Pulsatile Growth Hormone (GH) Secretion and Increased Process Irregularity in Women with Anorexia Nervosa: Indirect Evidence for Disruption of Feedback Regulation within the GH-Insulin-Like Growth Factor I Axis J. Clin. Endocrinol. Metab., June 1, 1999; 84(6): 2056 - 2063. [Abstract] [Full Text]

				M. S. Gill, A. A. Toogood, J. Jones, P. E. Clayton, and S. M. Shalet Serum Leptin Response to the Acute and Chronic Administration of Growth Hormone (GH) to Elderly Subjects with GH Deficiency J. Clin. Endocrinol. Metab., April 1, 1999; 84(4): 1288 - 1295. [Abstract] [Full Text]

				E. E. Muller, V. Locatelli, and D. Cocchi Neuroendocrine Control of Growth Hormone Secretion Physiol Rev, April 1, 1999; 79(2): 511 - 607. [Abstract] [Full Text] [PDF]

				A. A. Toogood and S. M. Shalet Growth Hormone Replacement Therapy in the Elderly with Hypothalamic-Pituitary Disease: A Dose-Finding Study J. Clin. Endocrinol. Metab., January 1, 1999; 84(1): 131 - 136. [Abstract] [Full Text]

				A. Giustina and J. D. Veldhuis Pathophysiology of the Neuroregulation of Growth Hormone Secretion in Experimental Animals and the Human Endocr. Rev., December 1, 1998; 19(6): 717 - 797. [Abstract] [Full Text]

				M. H. MacGillivray, S. L. Blethen, J. G. Buchlis, R. R. Clopper, D. E. Sandberg, and T. A. Conboy Current Dosing of Growth Hormone in Children With Growth Hormone Deficiency: How Physiologic? Pediatrics, August 1, 1998; 102(2): 527 - 530. [Abstract] [Full Text]

				Y. B. Sverrisdóttir, M. Elam, H. Herlitz, B.-A. Bengtsson, and G. Johannsson Intense Sympathetic Nerve Activity in Adults with Hypopituitarism and Untreated Growth Hormone Deficiency J. Clin. Endocrinol. Metab., June 1, 1998; 83(6): 1881 - 1885. [Abstract] [Full Text]

				J. A. Langlois, M. Visser, L. S. Davidovic, S. Maggi, G. Li, and T. B. Harris Hip Fracture Risk in Older White Men Is Associated With Change in Body Weight From Age 50 Years to Old Age Arch Intern Med, May 11, 1998; 158(9): 990 - 996. [Abstract] [Full Text] [PDF]

				R. Roubenoff, L. C. Rall, J. D. Veldhuis, J. J. Kehayias, C. Rosen, M. Nicolson, N. Lundgren, and S. Reichlin The Relationship between Growth Hormone Kinetics and Sarcopenia in Postmenopausal Women: The Role of Fat Mass and Leptin J. Clin. Endocrinol. Metab., May 1, 1998; 83(5): 1502 - 1506. [Abstract] [Full Text]

				S. M. Shalet, A. Toogood, A. Rahim, and B. M. D. Brennan The Diagnosis of Growth Hormone Deficiency in Children and Adults Endocr. Rev., April 1, 1998; 19(2): 203 - 223. [Abstract] [Full Text]

				C. J. Rosen and C. Conover Growth Hormone/Insulin-Like Growth Factor-I Axis in Aging: A Summary of a National Institutes of Aging-Sponsored Symposium J. Clin. Endocrinol. Metab., December 1, 1997; 82(12): 3919 - 3922. [Full Text] [PDF]

				N. Vahl, N. Moller, T. Lauritzen, J. S. Christiansen, and J. O. L. Jorgensen Metabolic Effects and Pharmacokinetics of a Growth Hormone Pulse in Healthy Adults: Relation to Age, Sex, and Body Composition J. Clin. Endocrinol. Metab., November 1, 1997; 82(11): 3612 - 3618. [Abstract] [Full Text] [PDF]

				R. G. Smith, L. H. T. Van der Ploeg, A. D. Howard, S. D. Feighner, K. Cheng, G. J. Hickey, M. J. Wyvratt Jr., M. H. Fisher, R. P. Nargund, and A. A. Patchett Peptidomimetic Regulation of Growth Hormone Secretion Endocr. Rev., October 1, 1997; 18(5): 621 - 645. [Abstract] [Full Text]

				M. Scacchi, A. I. Pincelli, A. Caumo, P. Tomasi, G. Delitala, G. Baldi, and F. Cavagnini Spontaneous Nocturnal Growth Hormone Secretion in Anorexia Nervosa J. Clin. Endocrinol. Metab., October 1, 1997; 82(10): 3225 - 3229. [Abstract] [Full Text] [PDF]

				Y. J. H. Janssen, P. Deurenberg, and F. Roelfsema Using Dilution Techniques and Multifrequency Bioelectrical Impedance to Assess Both Total Body Water and Extracellular Water at Baseline and During Recombinant Human Growth Hormone (GH) Treatment in GH-Deficient Adults J. Clin. Endocrinol. Metab., October 1, 1997; 82(10): 3349 - 3355. [Abstract] [Full Text] [PDF]

				M. Andersen, J. Hangaard, C. Hagen, G. Aimaretti, and E. Ghigo The Diagnosis of Growth Hormone Deficiency in Adults J. Clin. Endocrinol. Metab., October 1, 1997; 82(10): 3513 - 3514. [Full Text] [PDF]

				E. C. degli Uberti, M. R. Ambrosio, S. G. Cella, A. R. Margutti, G. Trasforini, A. E. Rigamonti, E. Petrone, and E. E. Muller Defective Hypothalamic Growth Hormone (GH)-Releasing Hormone Activity May Contribute to Declining GH Secretion with Age in Man J. Clin. Endocrinol. Metab., September 1, 1997; 82(9): 2885 - 2888. [Abstract] [Full Text] [PDF]

				I. M. Chapman, M. L. Hartman, S. S. Pezzoli, F. E. Harrell Jr., R. L. Hintz, K. G. M. M. Alberti, and M. O. Thorner Effect of Aging on the Sensitivity of Growth Hormone Secretion to Insulin-Like Growth Factor-I Negative Feedback J. Clin. Endocrinol. Metab., September 1, 1997; 82(9): 2996 - 3004. [Abstract] [Full Text] [PDF]

				C. H. Gravholt, R. W. Naeraa, S. Fisker, and J. S. Christiansen Body Composition and Physical Fitness Are Major Determinants of the Growth Hormone-Insulin-Like Growth Factor Axis Aberrations in Adult Turner's Syndrome, with Important Modulations by Treatment with 17{beta}-Estradiol J. Clin. Endocrinol. Metab., August 1, 1997; 82(8): 2570 - 2577. [Abstract] [Full Text] [PDF]

				P. C. Hindmarsh, C. H. D. Fall, P. J. Pringle, C. Osmond, and C. G. D. Brook Peak and Trough Growth Hormone Concentrations Have Different Associations with the Insulin-Like Growth Factor Axis, Body Composition, and Metabolic Parameters J. Clin. Endocrinol. Metab., July 1, 1997; 82(7): 2172 - 2176. [Abstract] [Full Text] [PDF]

				A. A. Toogood, R. M. Nass, S. S. Pezzoli, P. A. O'Neill, M. O. Thorner, and S. M. Shalet Preservation of Growth Hormone Pulsatility Despite Pituitary Pathology, Surgery, and Irradiation J. Clin. Endocrinol. Metab., July 1, 1997; 82(7): 2215 - 2221. [Abstract] [Full Text] [PDF]

				A. A. Toogood, J. E. Adams, P. A. O'Neill, and S. M. Shalet Elderly Patients with Adult-Onset Growth Hormone Deficiency Are Not Osteopenic J. Clin. Endocrinol. Metab., May 1, 1997; 82(5): 1462 - 1466. [Abstract] [Full Text] [PDF]

				G. Johannsson, MD, B.-A. Bengtsson, and Ph. D. Growth Hormone Therapy in GH-Deficient Adults: The Problem of the Dose--Authors' Response J. Clin. Endocrinol. Metab., April 1, 1997; 82(4): 1305 - 1306. [Full Text]

				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]

				Y. J. H. Janssen, M. Frolich, and F. Roelfsema A Low Starting Dose of Genotropin in Growth Hormone-Deficient Adults J. Clin. Endocrinol. Metab., January 1, 1997; 82(1): 129 - 135. [Abstract] [Full Text] [PDF]

				S. M. Pincus, T. Mulligan, A. Iranmanesh, S. Gheorghiu, M. Godschalk, and J. D. Veldhuis Older males secrete luteinizing hormone and testosterone more irregularly, and jointly more asynchronously, than younger males PNAS, November 26, 1996; 93(24): 14100 - 14105. [Abstract] [Full Text] [PDF]