Journal of Clinical Endocrinology & Metabolism, Vol 80, 3209-3222, Copyright © 1995 by Endocrine Society

ARTICLES

Differential impact of age, sex steroid hormones, and obesity on basal versus pulsatile growth hormone secretion in men as assessed in an ultrasensitive chemiluminescence assay

JD Veldhuis, AY Liem, S South, A Weltman, J Weltman, DA Clemmons, R Abbott, T Mulligan, ML Johnson and S Pincus
Department of Internal Medicine, University of Virginia Health Sciences Center, Charlottesville 22908, USA.

A chemiluminescence-based GH assay with 30- to 100-fold increased sensitivity recently disclosed combined basal and pulsatile GH secretion in men. However, how age, sex steroid hormones, and obesity singly and jointly influence the basal vs. pulsatile modes of GH release is not known. We used the foregoing assay (detection threshold, 0.002-0.005 microgram/L) and high sensitivity and specificity (> or = 90% each) deconvolution analysis to quantitate basal and pulsatile GH secretion from 24-h serum GH concentration profiles in 26 healthy lean and obese men, whose ages spanned 18-63 yr and whose percentage body fat ranged from 12-47%. Concentrations of serum insulin-like growth factor I (IGF-I), IGF-I-binding protein-1 (IGFBP-1), and IGFBP-3 were related to specific measures of basal or pulsatile GH release. We observed that mean (24-h) serum GH concentrations embraced a 140-fold range from 0.013-1.8 micrograms/L and were related negatively to age (r = -0.50; P < 0.01), percentage body fat (r = -0.620; P < 0.01), and their interaction (r = -0.610; P < 0.01). In contrast, testosterone was a robustly positive statistical determinant of mean serum GH values (r = 0.628; P = 0.0006). Stepwise multivariate regression analysis disclosed that percentage body fat alone and jointly with the serum testosterone concentration controlled, respectively, 38% and 50% of the total variability in GH levels (P = 0.0013 and P = 0.0008). As assessed by deconvolution analysis, GH secretory burst mass was negatively related to percentage body fat (r = -0.621; P < 0.01) and positively to serum testosterone (r = 0.529; P = 0.0054). The calculated half-life of GH correlated positively with serum estradiol (r = 0.447; P = 0.032), and negatively with percentage body fat (r = -0.437; P = 0.048). Basal GH secretion rates were negatively related to serum estradiol (r = - 0.485; P = 0.016). In contrast, GH secretory burst frequency and duration were unrelated to age, percentage body fat, or sex steroids. The fraction of total GH secreted in bursts was negatively correlated with the body mass index (r = -0.540; P < 0.01). Serum IGF-I concentrations were positively related to total pulsatile GH secretion (r = 0.690; P = 0.0011) and negatively to age (r = -0.597; P = 0.007) and percentage body fat (r = -0.611; P = 0.009).(ABSTRACT TRUNCATED AT 400 WORDS)

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				P. Rietschel, C. Hadigan, C. Corcoran, T. Stanley, G. Neubauer, J. Gertner, and S. Grinspoon Assessment of Growth Hormone Dynamics in Human Immunodeficiency Virus-Related Lipodystrophy J. Clin. Endocrinol. Metab., February 1, 2001; 86(2): 504 - 510. [Abstract] [Full Text]

				S. M. Anderson, N. Shah, W. S. Evans, J. T. Patrie, C. Y. Bowers, and J. D. Veldhuis Short-Term Estradiol Supplementation Augments Growth Hormone (GH) Secretory Responsiveness to Dose-Varying GH-Releasing Peptide Infusions in Healthy Postmenopausal Women J. Clin. Endocrinol. Metab., February 1, 2001; 86(2): 551 - 560. [Abstract] [Full Text]

				W. S. Evans, S. M. Anderson, L. T. Hull, P. P. Azimi, C. Y. Bowers, and J. D. Veldhuis Continuous 24-Hour Intravenous Infusion of Recombinant Human Growth Hormone (GH)-Releasing Hormone-(1-44)-Amide Augments Pulsatile, Entropic, and Daily Rhythmic GH Secretion in Postmenopausal Women Equally in the Estrogen-Withdrawn and Estrogen-Supplemented States J. Clin. Endocrinol. Metab., February 1, 2001; 86(2): 700 - 712. [Abstract] [Full Text]

				S. R. Peacey, A. A. Toogood, J. D. Veldhuis, M. O. Thorner, and S. M. Shalet The Relationship between 24-Hour Growth Hormone Secretion and Insulin-Like Growth Factor I in Patients with Successfully Treated Acromegaly: Impact of Surgery or Radiotherapy J. Clin. Endocrinol. Metab., January 1, 2001; 86(1): 259 - 266. [Abstract] [Full Text]

				M. Russell-Aulet, E. V. Dimaraki, C. A. Jaffe, R. DeMott-Friberg, and A. L. Barkan Aging-Related Growth Hormone (GH) Decrease Is a Selective Hypothalamic GH-Releasing Hormone Pulse Amplitude Mediated Phenomenon J. Gerontol. A Biol. Sci. Med. Sci., January 1, 2001; 56(2): 124M - 129. [Abstract] [Full Text]

				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]

				M. Bergendahl, A. Iranmanesh, C. Pastor, W. S. Evans, and J. D. Veldhuis Homeostatic Joint Amplification of Pulsatile and 24-Hour Rhythmic Cortisol Secretion by Fasting Stress in Midluteal Phase Women: Concurrent Disruption of Cortisol-Growth Hormone, Cortisol-Luteinizing Hormone, and Cortisol-Leptin Synchrony J. Clin. Endocrinol. Metab., November 1, 2000; 85(11): 4028 - 4035. [Abstract] [Full Text]

				L. Wideman, J. Y. Weltman, J. T. Patrie, C. Y. Bowers, N. Shah, S. Story, A. Weltman, and J. D. Veldhuis Synergy of L-arginine and growth hormone (GH)-releasing peptide-2 on GH release: influence of gender Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2000; 279(4): R1455 - R1466. [Abstract] [Full Text] [PDF]

				H. Yu and T. Rohan Role of the Insulin-Like Growth Factor Family in Cancer Development and Progression J Natl Cancer Inst, September 20, 2000; 92(18): 1472 - 1489. [Abstract] [Full Text] [PDF]

				A. Weltman, C. J. Pritzlaff, L. Wideman, J. Y. Weltman, J. L. Blumer, R. D. Abbott, M. L. Hartman, and J. D. Veldhuis Exercise-dependent growth hormone release is linked to markers of heightened central adrenergic outflow J Appl Physiol, August 1, 2000; 89(2): 629 - 635. [Abstract] [Full Text] [PDF]

				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]

				S. M. Pincus, J. D. Veldhuis, and A. D. Rogol Longitudinal changes in growth hormone secretory process irregularity assessed transpubertally in healthy boys Am J Physiol Endocrinol Metab, August 1, 2000; 279(2): E417 - E424. [Abstract] [Full Text] [PDF]

				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]

				M. Bergendahl, A. Iranmanesh, T. Mulligan, and J. D. Veldhuis Impact of Age on Cortisol Secretory Dynamics Basally and as Driven by Nutrient-Withdrawal Stress J. Clin. Endocrinol. Metab., June 1, 2000; 85(6): 2203 - 2214. [Abstract] [Full Text]

				J. D. Veldhuis, A. Iranmanesh, M. Godschalk, and T. Mulligan Older Men Manifest Multifold Synchrony Disruption of Reproductive Neurohormone Outflow J. Clin. Endocrinol. Metab., April 1, 2000; 85(4): 1477 - 1486. [Abstract] [Full Text]

				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]

				G. A. Bray and F. L. Greenway Current and Potential Drugs for Treatment of Obesity Endocr. Rev., December 1, 1999; 20(6): 805 - 875. [Abstract] [Full Text]

				Discontinuation of Growth Hormone (GH) Treatment: Metabolic Effects in GH-Deficient and GH-Sufficient Adolescent Patients Compared with Control Subjects J. Clin. Endocrinol. Metab., December 1, 1999; 84(12): 4516 - 4524. [Abstract] [Full Text]

				S. M. Pincus, M. L. Hartman, F. Roelfsema, M. O. Thorner, and J. D. Veldhuis Hormone pulsatility discrimination via coarse and short time sampling Am J Physiol Endocrinol Metab, November 1, 1999; 277(5): E948 - E957. [Abstract] [Full Text] [PDF]

				J. D. Veldhuis, Ali Iranmanesh, Thomas Mulligan, and Steven M. Pincus Disruption of the Young-Adult Synchrony between Luteinizing Hormone Release and Oscillations in Follicle-Stimulating Hormone, Prolactin, and Nocturnal Penile Tumescence (NPT) in Healthy Older Men J. Clin. Endocrinol. Metab., October 1, 1999; 84(10): 3498 - 3505. [Abstract] [Full Text] [PDF]

				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]

				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]

				J. A. Kanaley, M. M. Weatherup-Dentes, E. B. Jaynes, and M. L. Hartman Obesity Attenuates the Growth Hormone Response to Exercise J. Clin. Endocrinol. Metab., September 1, 1999; 84(9): 3156 - 3161. [Abstract] [Full Text]

				G. M. Bright, J. D. Veldhuis, A. Iranmanesh, G. Baumann, H. Maheshwari, and J. Lima Appraisal of Growth Hormone (GH) Secretion: Evaluation of a Composite Pharmacokinetic Model That Discriminates Multiple Components of GH Input J. Clin. Endocrinol. Metab., September 1, 1999; 84(9): 3301 - 3308. [Abstract] [Full Text]

				C. J. Pritzlaff, L. Wideman, J. Y. Weltman, R. D. Abbott, M. E. Gutgesell, M. L. Hartman, J. D. Veldhuis, and A. Weltman Impact of acute exercise intensity on pulsatile growth hormone release in men J Appl Physiol, August 1, 1999; 87(2): 498 - 504. [Abstract] [Full Text] [PDF]

				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]

				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]

				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]

				J. Svensson, J.-O. Jansson, M. Ottosson, G. Johannsson, M.-R. Taskinen, O. Wiklund, and B.-A. Bengtsson Treatment of Obese Subjects with the Oral Growth Hormone Secretagogue MK-677 Affects Serum Concentrations of Several Lipoproteins, But Not Lipoprotein(a) J. Clin. Endocrinol. Metab., June 1, 1999; 84(6): 2028 - 2033. [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]

				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]

				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]

				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]

				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]