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Journal of Clinical Endocrinology & Metabolism Vol. 73, No. 5 1081-1088
doi:10.1210/jcem-73-5-1081
Copyright © 1991 by the Endocrine Society.
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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*

ALI IRANMANESH, GERMAN LIZARRALDE and JOHANNES D. VELDHUIS

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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Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
J. G. Langendonk, J. D. Veldhuis, J. Burggraaf, R. C. Schoemaker, A. F. Cohen, A. Edo Meinders, and H. Pijl
Estimation of growth hormone secretion rate: impact of kinetic assumptions intrinsic to the analytical approach
Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2001; 280(1): R225 - R232.
[Abstract] [Full Text] [PDF]


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J. Clin. Endocrinol. Metab.Home page
P. Sytze van Dam, H. E. C. Smid, W. R. de Vries, M. Niesink, E. Bolscher, E. J. Waasdorp, C. Dieguez, F. F. Casanueva, and H. P. F. Koppeschaar
Reduction of Free Fatty Acids By Acipimox Enhances the Growth Hormone (GH) Responses to GH-Releasing Peptide 2 in Elderly Men
J. Clin. Endocrinol. Metab., December 1, 2000; 85(12): 4706 - 4711.
[Abstract] [Full Text]


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J. Clin. Endocrinol. Metab.Home page
R. Fernholm, M. Bramnert, E. Hägg, A. Hilding, D. J. Baylink, S. Mohan, and M. Thorén
Growth Hormone Replacement Therapy Improves Body Composition and Increases Bone Metabolism in Elderly Patients with Pituitary Disease
J. Clin. Endocrinol. Metab., November 1, 2000; 85(11): 4104 - 4112.
[Abstract] [Full Text]


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J. Clin. Endocrinol. Metab.Home page
A. M. Isidori, F. Strollo, M. Morè, M. Caprio, A. Aversa, C. Moretti, G. Frajese, G. Riondino, and A. Fabbri
Leptin and Aging: Correlation with Endocrine Changes in Male and Female Healthy Adult Populations of Different Body Weights
J. Clin. Endocrinol. Metab., May 1, 2000; 85(5): 1954 - 1962.
[Abstract] [Full Text]


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J. Clin. Endocrinol. Metab.Home page
B.-A. Bengtsson and G. Johannsson
The Treatment of Growth Hormone Deficiency in Adults
J. Clin. Endocrinol. Metab., March 1, 2000; 85(3): 933 - 937.
[Full Text]


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J. Clin. Endocrinol. Metab.Home page
G. Van den Berghe, R. C. Baxter, F. Weekers, P. Wouters, C. Y. Bowers, and J. D. Veldhuis
A Paradoxical Gender Dissociation within the Growth Hormone/Insulin-Like Growth Factor I Axis during Protracted Critical Illness
J. Clin. Endocrinol. Metab., January 1, 2000; 85(1): 183 - 192.
[Abstract] [Full Text]


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J. Clin. Endocrinol. Metab.Home page
D. M. Cook, W. H. Ludlam, and M. B. Cook
Route of Estrogen Administration Helps to Determine Growth Hormone (GH) Replacement Dose in GH-Deficient Adults
J. Clin. Endocrinol. Metab., November 1, 1999; 84(11): 3956 - 3960.
[Abstract] [Full Text]


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Am. J. Physiol. Endocrinol. Metab.Home page
J. G. Langendonk, A. E. Meinders, J. Burggraaf, M. Frolich, C. A. M. Roelen, R. C. Schoemaker, A. F. Cohen, and H. Pijl
Influence of obesity and body fat distribution on growth hormone kinetics in humans
Am J Physiol Endocrinol Metab, November 1, 1999; 277(5): E824 - E829.
[Abstract] [Full Text] [PDF]


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J. Clin. Endocrinol. Metab.Home page
H. Fors, H. Matsuoka, I. Bosaeus, S. Rosberg, K. A. Wikland, and R. Bjarnason
Serum Leptin Levels Correlate with Growth Hormone Secretion and Body Fat in Children
J. Clin. Endocrinol. Metab., October 1, 1999; 84(10): 3586 - 3590.
[Abstract] [Full Text] [PDF]


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J. Clin. Endocrinol. Metab.Home page
J. D. Wallace, R. C. Cuneo, R. Baxter, H. Orskov, N. Keay, C. Pentecost, R. Dall, T. Rosen, J. O. Jorgensen, A. Cittadini, et al.
Responses of the Growth Hormone (GH) and Insulin-Like Growth Factor Axis to Exercise, GH Administration, and GH Withdrawal in Trained Adult Males: A Potential Test for GH Abuse in Sport
J. Clin. Endocrinol. Metab., October 1, 1999; 84(10): 3591 - 3601.
[Abstract] [Full Text] [PDF]


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J. Clin. Endocrinol. Metab.Home page
P. C. Hindmarsh, E. Dennison, S. M. Pincus, C. Cooper, C. H. D. Fall, D. R. Matthews, P. J. Pringle, and C. G. D. Brook
A Sexually Dimorphic Pattern of Growth Hormone Secretion in the Elderly
J. Clin. Endocrinol. Metab., August 1, 1999; 84(8): 2679 - 2685.
[Abstract] [Full Text]


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Am. J. Physiol. Endocrinol. Metab.Home page
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]


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J. Clin. Endocrinol. Metab.Home page
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]


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J. Clin. Endocrinol. Metab.Home page
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]


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J. Clin. Endocrinol. Metab.Home page
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]


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J. Clin. Endocrinol. Metab.Home page
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]


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Physiol. Rev.Home page
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]


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J. Clin. Endocrinol. Metab.Home page
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]


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Endocr. Rev.Home page
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]


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PediatricsHome page
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]


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J. Clin. Endocrinol. Metab.Home page
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]


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Arch Intern MedHome page
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]


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J. Clin. Endocrinol. Metab.Home page
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]


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Endocr. Rev.Home page
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]


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J. Clin. Endocrinol. Metab.Home page
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]


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J. Clin. Endocrinol. Metab.Home page
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]


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Endocr. Rev.Home page
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]


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J. Clin. Endocrinol. Metab.Home page
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]


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J. Clin. Endocrinol. Metab.Home page
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]


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J. Clin. Endocrinol. Metab.Home page
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]


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J. Clin. Endocrinol. Metab.Home page
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]


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J. Clin. Endocrinol. Metab.Home page
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]


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J. Clin. Endocrinol. Metab.Home page
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]


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J. Clin. Endocrinol. Metab.Home page
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]


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J. Clin. Endocrinol. Metab.Home page
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]


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J. Clin. Endocrinol. Metab.Home page
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]


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J. Clin. Endocrinol. Metab.Home page
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]


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J. Clin. Endocrinol. Metab.Home page
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]


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J. Clin. Endocrinol. Metab.Home page
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]


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Proc. Natl. Acad. Sci. USAHome page
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]




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