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Journal of Clinical Endocrinology & Metabolism, Vol 81, 2460-2467, Copyright © 1996 by Endocrine Society

ARTICLES

An amplitude-specific divergence in the pulsatile mode of growth hormone (GH) secretion underlies the gender difference in mean GH concentrations in men and premenopausal women

G van den Berg, JD Veldhuis, M Frolich and F Roelfsema
Department of Endocrinology, University Hospital, Leiden, The Netherlands.

Although many studies have discerned higher serum GH concentrations in women than in men, based on measurements of single random blood samples or integrated 24-h means, the neuroendocrine mechanisms that underlie such gender differences have not been defined. Such mechanisms might entail an increase in GH-secretory burst frequency, amplitude, or duration, heightened interpulse basal GH release, or a prolonged half- life of GH. These mechanisms can be distinguished by deconvolution analysis of appropriate GH time series. Earlier studies employed RIA or IRMA with sensitivities of 0.1-0.5 microgram/L, which result in frequently undetectable serum GH concentrations. To address these limitations, we undertook blood sampling at 10-min intervals for 24 h and applied a high-sensitivity immunofluorometric assay of GH (sensitivity 0.0115 microgram/L). Multiparameter deconvolution analysis was used to estimate specific features of GH secretion, while simultaneously calculating the half-life of endogenous GH. Eleven men and 11 premenopausal women from the same community were studied. Discrete peak detection by Cluster was employed as a complementary half- life-independent technique to assign variations in serum GH into pulsatile and basal fractions over 24 h. Cluster revealed significantly higher mean serum GH concentrations over 24 h in women (0.78 +/- 0.08 microgram/L) compared with in men (0.27 +/- 0.03 microgram/L, P < 0.00005). Women exhibited significantly higher maximal serum GH concentration peak values than men (2.08 +/- 0.34 microgram/L in women, 0.67 +/- 0.11 microgram/L in men, P = 0.0008), which could be, in turn, attributed to a significantly increased incremental serum GH peak amplitude (1.85 +/- 0.33 microgram/L in women vs. 0.60 +/- 0.10 microgram/L in men, P = 0.0021) and a longer peak duration (114 +/- 8 min in women, 86 +/- 4 min in men, P = 0.008). The mean area under the serum GH concentration peak was significantly (3-fold) higher in women than in men (98 +/- 17 micrograms/L.min in women, 34 +/- 8 micrograms/L.min in men, P = 0.0046). Serum GH peak frequency was similar in women (9.7 +/- 0.8 peak/24 h) and men (10.7 +/- 1.1 peak/24 h, P = NS). The mechanisms underlying the increase in serum GH concentration pulse amplitude, duration, and area were investigated further by deconvolution analysis. Deconvolution analysis disclosed equivalent secretory pulse frequencies in women and men (13 +/- 0.9 bursts/day in women, 10.5 +/- 1.3 bursts/day in men,P = NS), and statistically indistinguishable mean interburst intervals of 106 +/- 8 min in women and 150 +/- 26 min in men (P = NS). GH-secretory burst mass was significantly higher in women by approximately 2.4-fold (P = 0.0013) compared with in men, which was attributed to a greater burst amplitude. Only low levels of basal GH release were inferred in women (5%) and men (9%), which did not differ significantly between genders. Moreover, the calculated half-life of endogenous GH was no different in women compared with in men: 15.8 +/- 0.7 min vs. 17.1 +/- 0.8 min, respectively (P = NS). The calculated daily secretion rate was 3-fold higher in women (47 +/- 4.8 micrograms/L.24 h) than in men (15 +/- 1.8 micrograms/L.24 h) (P < 0.001). In summary, discrete peak-detection analysis of serum GH concentration profiles collected at 10-min intervals over 24 h in men and premenopausal women discloses significantly different mean serum GH concentrations that are accounted for by higher maximal and incremental serum GH peak amplitudes. Deconvolution analysis demonstrated that the mechanism supporting the amplitude-specific difference in women was an augmentation of the GH- secretory burst mass caused by a higher GH-secretory burst amplitude. These gender differences were highly specific because the frequency of detectable GH-secretory bursts, the calculated endogenous half-life, and the estimated basal GH release were no different in women than in men.


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Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2000; 279(4): R1455 - R1466.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
N. Shah, W. S. Evans, C. Y. Bowers, and J. D. Veldhuis
Oral Estradiol Administration Modulates Continuous Intravenous Growth Hormone (GH)-Releasing Peptide-2-Driven GH Secretion in Postmenopausal Women
J. Clin. Endocrinol. Metab., August 1, 2000; 85(8): 2649 - 2659.
[Abstract] [Full Text]

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 J. Clin. Endocrinol. Metab.Home page
J. D. Veldhuis, J. N. Roemmich, and A. D. Rogol
Gender and Sexual Maturation-Dependent Contrasts in the Neuroregulation of Growth Hormone Secretion in Prepubertal and Late Adolescent Males and Females--A General Clinical Research Center-Based Study
J. Clin. Endocrinol. Metab., July 1, 2000; 85(7): 2385 - 2394.
[Abstract] [Full Text]

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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
D. M. Keenan and J. D. Veldhuis
Explicating hypergonadotropism in postmenopausal women: a statistical model
Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2000; 278(5): R1247 - R1257.
[Abstract] [Full Text] [PDF]

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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
J. P. T. Span, G. F. F. M. Pieters, C. G. J. Sweep, A. R. M. M. Hermus, and A. G. H. Smals
Gender Difference in Insulin-Like Growth Factor I Response to Growth Hormone (GH) Treatment in GH-Deficient Adults: Role of Sex Hormone Replacement
J. Clin. Endocrinol. Metab., March 1, 2000; 85(3): 1121 - 1125.
[Abstract] [Full Text]

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 J. Clin. Endocrinol. Metab.Home page
Y. Hashimoto, T. Kamioka, M. Hosaka, K. Mabuchi, A. Mizuchi, Y. Shimazaki, M. Tsunoo, and T. Tanaka
Exogenous 20K Growth Hormone (GH) Suppresses Endogenous 22K GH Secretion in Normal Men
J. Clin. Endocrinol. Metab., February 1, 2000; 85(2): 601 - 606.
[Abstract] [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
Y. J. H. Janssen, F. Helmerhorst, M. Frölich, and F. Roelfsema
A Switch from Oral (2 mg/Day) to Transdermal (50 {micro}g/Day) 17{beta}-Estradiol Therapy Increases Serum Insulin-Like Growth Factor-I Levels in Recombinant Human Growth Hormone (GH)-Substituted Women with GH Deficiency
J. Clin. Endocrinol. Metab., January 1, 2000; 85(1): 464 - 467.
[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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 J. Appl. Physiol.Home page
L. Wideman, J. Y. Weltman, N. Shah, S. Story, J. D. Veldhuis, and A. Weltman
Effects of gender on exercise-induced growth hormone release
J Appl Physiol, September 1, 1999; 87(3): 1154 - 1162.
[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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 J. Clin. Endocrinol. Metab.Home page
N. Shah, J. Aloi, W. S. Evans, and J. D. Veldhuis
Time Mode of Growth Hormone (GH) Entry into the Bloodstream and Steady-State Plasma GH Concentrations, Rather Than Sex, Estradiol, or Menstrual Cycle Stage, Primarily Determine the GH Elimination Rate in Healthy Young Women and Men
J. Clin. Endocrinol. Metab., August 1, 1999; 84(8): 2862 - 2869.
[Abstract] [Full Text]

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 Clin. Chem.Home page
B. Eden Engstrom, F. A. Karlsson, and L. Wide
Gender Differences in Diurnal Growth Hormone and Epinephrine Values in Young Adults during Ambulation
Clin. Chem., August 1, 1999; 45(8): 1235 - 1239.
[Abstract] [Full Text] [PDF]

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A. G. Johansson, B. E. Engström, S. Ljunghall, F. A. Karlsson, and P. Burman
Gender Differences in the Effects of Long Term Growth Hormone (GH) Treatment on Bone in Adults with GH Deficiency
J. Clin. Endocrinol. Metab., June 1, 1999; 84(6): 2002 - 2007.
[Abstract] [Full Text]

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 J. Clin. Endocrinol. Metab.Home page
N. Shah, W. S. Evans, C. Y. Bowers, and J. D. Veldhuis
Tripartite Neuroendocrine Activation of the Human Growth Hormone (GH) Axis in Women by Continuous 24-Hour GH-Releasing Peptide Infusion: Pulsatile, Entropic, and Nyctohemeral Mechanisms
J. Clin. Endocrinol. Metab., June 1, 1999; 84(6): 2140 - 2150.
[Abstract] [Full Text]

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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
N. Shah, W. S. Evans, and J. D. Veldhuis
Actions of estrogen on pulsatile, nyctohemeral, and entropic modes of growth hormone secretion
Am J Physiol Regulatory Integrative Comp Physiol, May 1, 1999; 276(5): R1351 - R1358.
[Abstract] [Full Text] [PDF]

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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
M. Bergendahl, W. S. Evans, C. Pastor, A. Patel, A. Iranmanesh, and J. D. Veldhuis
Short-Term Fasting Suppresses Leptin and (Conversely) Activates Disorderly Growth Hormone Secretion in Midluteal Phase Women--A Clinical Research Center Study
J. Clin. Endocrinol. Metab., March 1, 1999; 84(3): 883 - 894.
[Abstract] [Full Text]

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 Clin. Chem.Home page
E. Cappellin, R. Gatti, and E. F. De Palo
Influence of Gender in Growth Hormone Status in Adults: Role of Urinary Growth Hormone
Clin. Chem., March 1, 1999; 45(3): 443 - 444.
[Full Text] [PDF]

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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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 J. Clin. Endocrinol. Metab.Home page
W. M. Drake, D. Coyte, C. Camacho-Hübner, N. M. Jivanji, G. Kaltsas, D. F. Wood, P. J. Trainer, A. B. Grossman, G. M. Besser, and J. P. Monson
Optimizing Growth Hormone Replacement Therapy by Dose Titration in Hypopituitary Adults
J. Clin. Endocrinol. Metab., November 1, 1998; 83(11): 3913 - 3919.
[Abstract] [Full Text]

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 Clin. Chem.Home page
B. E. Engstrom, F. A. Karlsson, and L. Wide
Marked gender differences in ambulatory morning growth hormone values in young adults
Clin. Chem., June 1, 1998; 44(6): 1289 - 1295.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
J. N. Roemmich, P. A. Clark, V. Mai, S. S. Berr, A. Weltman, J. D. Veldhuis, and A. D. Rogol
Alterations in Growth and Body Composition During Puberty: III. Influence of Maturation, Gender, Body Composition, Fat Distribution, Aerobic Fitness, and Energy Expenditure on Nocturnal Growth Hormone Release
J. Clin. Endocrinol. Metab., May 1, 1998; 83(5): 1440 - 1447.
[Abstract] [Full Text]

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P. Ovesen, N. Vahl, S. Fisker, J. D. Veldhuis, J. S. Christiansen, and J. O. L. Jørgensen
Increased Pulsatile, But Not Basal, Growth Hormone Secretion Rates and Plasma Insulin-Like Growth Factor I Levels during the Periovulatory Interval in Normal Women
J. Clin. Endocrinol. Metab., May 1, 1998; 83(5): 1662 - 1667.
[Abstract] [Full Text]

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P. Lucidi, M. Lauteri, S. Laureti, R. Celleno, S. Santoni, E. Volpi, G. Angeletti, F. Santeusanio, and P. De Feo
A Dose-Response Study of Growth Hormone (GH) Replacement on Whole Body Protein and Lipid Kinetics in GH-Deficient Adults
J. Clin. Endocrinol. Metab., February 1, 1998; 83(2): 353 - 357.
[Abstract] [Full Text]

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 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
E. Gevers, S. M. Pincus, I. C. A. F. Robinson, and J. D. Veldhuis
Differential orderliness of the GH release process in castrate male and female rats
Am J Physiol Regulatory Integrative Comp Physiol, February 1, 1998; 274(2): R437 - R444.
[Abstract] [Full Text] [PDF]

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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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S. Grinspoon, C. Corcoran, K. Miller, B. M. K. Biller, H. Askari, E. Wang, J. Hubbard, E. J. Anderson, N. Basgoz, H. M. Heller, et al.
Body Composition and Endocrine Function in Women with Acquired Immunodeficiency Syndrome Wasting
J. Clin. Endocrinol. Metab., May 1, 1997; 82(5): 1332 - 1337.
[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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 J. Appl. Physiol.Home page
C. J. Pritzlaff-Roy, L. Widemen, J. Y. Weltman, R. Abbott, M. Gutgesell, M. L. Hartman, J. D. Veldhuis, and A. Weltman
Gender governs the relationship between exercise intensity and growth hormone release in young adults
J Appl Physiol, May 1, 2002; 92(5): 2053 - 2060.
[Abstract] [Full Text] [PDF]


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