This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Russell-Aulet, M. Articles by Barkan, A. L. Search for Related Content PubMed PubMed Citation Articles by Russell-Aulet, M. Articles by Barkan, A. L.

In Vivo Semiquantification of Hypothalamic Growth Hormone-Releasing Hormone (GHRH) Output in Humans: Evidence for Relative GHRH Deficiency in Aging¹

Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Michigan Medical Center, and Department of Veterans Affairs Medical Center, Ann Arbor, Michigan 48109-0354

Address all correspondence and requests for reprints to: Ariel L Barkan, M.D, 3920 Taubman Center, Box 0354, University of Michigan Medical Center, Ann Arbor, Michigan 48109-0354. E-mail: abarkan{at}umich.edu

GH secretion declines with aging. The neuroendocrine mechanisms of somatopause are uncertain. To semiquantify endogenous hypothalamic GHRH output, we measured the suppressibility of spontaneous and GHRH-stimulated GH secretion by graded doses of a specific competitive GHRH receptor antagonist (N-Ac-Tyr¹,D-Arg²)GHRH-(1–29) in healthy young and elderly men. Nocturnal GH was about 30% lower in the elderly than in the young. Graded boluses of GHRH elicited dose-dependent GH responses, with no difference between the two age groups. Graded infusions of GHRH antagonist suppressed GH responses to GHRH in a dose-dependent manner, but with similar potency in both groups. The degree of inhibition depended on the magnitude of GHRH bolus: the dose-inhibition curves for the low GHRH boluses were shifted to the left compared to those with the high GHRH bolus (P = 0.01). Similarly, the dose-inhibition curve for spontaneous GH secretion was shifted to the left for the elderly compared to the young men (P = 0.01). Thus, the model of graded infusions of GHRH antagonist differentiates between different amounts of GHRH presented to the pituitary, permitting semiquantification of the endogenous hypothalamic GHRH output in vivo. Our data suggest that there is an age-dependent decrease in the endogenous hypothalamic GHRH output contributing to the age-associated GH decline.

This article has been cited by other articles:

				S. Surya, J. F. Horowitz, N. Goldenberg, A. Sakharova, M. Harber, A. S. Cornford, K. Symons, and A. L. Barkan The Pattern of Growth Hormone Delivery to Peripheral Tissues Determines Insulin-Like Growth Factor-1 and Lipolytic Responses in Obese Subjects J. Clin. Endocrinol. Metab., August 1, 2009; 94(8): 2828 - 2834. [Abstract] [Full Text] [PDF]

				A. A. Sakharova, J. F. Horowitz, S. Surya, N. Goldenberg, M. P. Harber, K. Symons, and A. Barkan Role of Growth Hormone in Regulating Lipolysis, Proteolysis, and Hepatic Glucose Production during Fasting J. Clin. Endocrinol. Metab., July 1, 2008; 93(7): 2755 - 2759. [Abstract] [Full Text] [PDF]

				J. D. Veldhuis, D. M. Keenan, and C. Y. Bowers Estimation of the size and shape of GH secretory bursts in healthy women using a physiological estradiol clamp and variable-waveform deconvolution model Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2007; 293(3): R1013 - R1021. [Abstract] [Full Text] [PDF]

				M. Iruthayanathan, Y.-H. Zhou, and G. V. Childs Dehydroepiandrosterone Restoration of Growth Hormone Gene Expression in Aging Female Rats, in Vivo and in Vitro: Evidence for Actions via Estrogen Receptors Endocrinology, December 1, 2005; 146(12): 5176 - 5187. [Abstract] [Full Text] [PDF]

				J. D. Veldhuis, J. Y. Weltman, A. L. Weltman, A. Iranmanesh, E. E. Muller, and C. Y. Bowers Age and Secretagogue Type Jointly Determine Dynamic Growth Hormone Responses to Exogenous Insulin-Like Growth Factor-Negative Feedback in Healthy Men J. Clin. Endocrinol. Metab., November 1, 2004; 89(11): 5542 - 5548. [Abstract] [Full Text] [PDF]

				J. J. Orrego, E. Dimaraki, K. Symons, and A. L. Barkan Physiological Testosterone Replenishment in Healthy Elderly Men Does Not Normalize Pituitary Growth Hormone Output: Evidence against the Connection between Senile Hypogonadism and Somatopause J. Clin. Endocrinol. Metab., July 1, 2004; 89(7): 3255 - 3260. [Abstract] [Full Text] [PDF]

				M. S. Racine, K. V. Symons, C. M. Foster, and A. L. Barkan Augmentation of Growth Hormone Secretion after Testosterone Treatment in Boys with Constitutional Delay of Growth and Adolescence: Evidence against an Increase in Hypothalamic Secretion of Growth Hormone-Releasing Hormone J. Clin. Endocrinol. Metab., July 1, 2004; 89(7): 3326 - 3331. [Abstract] [Full Text] [PDF]

				S. K. Jessup, E. V. Dimaraki, K. V. Symons, and A. L. Barkan Sexual Dimorphism of Growth Hormone (GH) Regulation in Humans: Endogenous GH-Releasing Hormone Maintains Basal GH in Women But Not in Men J. Clin. Endocrinol. Metab., October 1, 2003; 88(10): 4776 - 4780. [Abstract] [Full Text] [PDF]

				A. L. Barkan, E. V. Dimaraki, S. K. Jessup, K. V. Symons, M. Ermolenko, and C. A. Jaffe Ghrelin Secretion in Humans Is Sexually Dimorphic, Suppressed by Somatostatin, and Not Affected by the Ambient Growth Hormone Levels J. Clin. Endocrinol. Metab., May 1, 2003; 88(5): 2180 - 2184. [Abstract] [Full Text] [PDF]

				S. Nakamura, M. Mizuno, H. Katakami, A. C. Gore, and E. Terasawa Aging-Related Changes in in Vivo Release of Growth Hormone-Releasing Hormone and Somatostatin from the Stalk-Median Eminence in Female Rhesus Monkeys (Macaca mulatta) J. Clin. Endocrinol. Metab., February 1, 2003; 88(2): 827 - 833. [Abstract] [Full Text] [PDF]

				J. J. Orrego, M. Russell-Aulet, R. Demott-Friberg, and A. L. Barkan Semiquantification of Hypothalamic GH-Releasing Hormone Output in Women: Evidence for Sexual Dimorphism in the Mechanism of the Somatopause J. Clin. Endocrinol. Metab., November 1, 2001; 86(11): 5485 - 5490. [Abstract] [Full Text] [PDF]

				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]

				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]