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Pathophysiology of the Neuroregulation of Growth Hormone Secretion in Experimental Animals and the Human¹

Endocrine Section (A.G.), Department of Internal Medicine, University of Brescia, 25125 Brescia, Italy; and Division of Endocrinology (J.D.V.), Department of Internal Medicine and National Science Foundation Center in Biological Timing, University of Virginia, Charlottesville, Virginia 22908

I. Introduction

II. Contemporary Tools for Neuroendocrinological Investigation of the GH Axis

A. Genetic, molecular, and transgenic models

B. Human GH rhythms

III. Neuropeptide Regulation of the GH Axis: Somatostatin and GHRH

A. Mechanism of somatostatin actions and its receptors

B. Human somatostatin receptor

C. GHRH

D. Feedback regulation of GH secretion

IV. Other GH-Regulating Neuropeptides

A. GH-releasing peptides (GHRPs)

B. Galanin

C. Calcitonin

D. PACAP

E. Opioid peptides

F. TRH

G. Neuropeptide Y

H. Substance P

I. Bombesin

J. Melatonin

K. Other GH secretagogues

V. Neurotransmitter Regulation of GH Secretion

A. Interspecies differences

B. Acetylcholine and catecholamines

C. Other neurotransmitters

VI. Role of Metabolic Substrates in the Regulation of the GH Axis

A. Blood glucose

B. Leptin and FFA

C. Amino acids

VII. Other Hormonal Regulators of the GH Axis

A. Glucocorticoids

B. Gonadal sex hormones

C. Thyroid hormones

VIII. Regulation of the GH Axis Throughout the Human Lifetime

A. Birth and infancy

B. Prepuberty

C. Puberty

D. Adulthood

E. Aging

F. GH treatment in older humans

IX. Exercise’s Modulation of the GH Axis

A. Experimental animals

B. Humans

C. Neural control of GH release during exercise

D. Kinetics of exercise-induced GH release

X. Summary

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				J. D. Veldhuis, A. Iranmanesh, and C. Y. Bowers Joint Mechanisms of Impaired Growth-Hormone Pulse Renewal in Aging Men J. Clin. Endocrinol. Metab., July 1, 2005; 90(7): 4177 - 4183. [Abstract] [Full Text] [PDF]

				A. Gambineri, L. Patton, R. De Iasio, B. Cantelli, G. E. Cognini, M. Filicori, A. Barreca, E. Diamanti-Kandarakis, U. Pagotto, and R. Pasquali Efficacy of Octreotide-LAR in Dieting Women with Abdominal Obesity and Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., July 1, 2005; 90(7): 3854 - 3862. [Abstract] [Full Text] [PDF]

				N. Mauras, O. H. Pescovitz, V. Allada, M. Messig, M. P. Wajnrajch, B. Lippe, and on behalf of the Transition Study Group Limited Efficacy of Growth Hormone (GH) during Transition of GH-Deficient Patients from Adolescence to Adulthood: A Phase III Multicenter, Double-Blind, Randomized Two-Year Trial J. Clin. Endocrinol. Metab., July 1, 2005; 90(7): 3946 - 3955. [Abstract] [Full Text] [PDF]

				L. Jette, R. Leger, K. Thibaudeau, C. Benquet, M. Robitaille, I. Pellerin, V. Paradis, P. van Wyk, K. Pham, and D. P. Bridon Human Growth Hormone-Releasing Factor (hGRF)1-29-Albumin Bioconjugates Activate the GRF Receptor on the Anterior Pituitary in Rats: Identification of CJC-1295 as a Long-Lasting GRF Analog Endocrinology, July 1, 2005; 146(7): 3052 - 3058. [Abstract] [Full Text] [PDF]

				P. Y. Liu, S. M. Pincus, D. M. Keenan, F. Roelfsema, and J. D. Veldhuis Joint synchrony of reciprocal hormonal signaling in human paradigms of both ACTH excess and cortisol depletion Am J Physiol Endocrinol Metab, July 1, 2005; 289(1): E160 - E165. [Abstract] [Full Text] [PDF]

				L. S. Farhy and J. D. Veldhuis Deterministic construct of amplifying actions of ghrelin on pulsatile growth hormone secretion Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2005; 288(6): R1649 - R1663. [Abstract] [Full Text] [PDF]

				A. M. Avram, C. A. Jaffe, K. V. Symons, and A. L. Barkan Endogenous Circulating Ghrelin Does Not Mediate Growth Hormone Rhythmicity or Response to Fasting J. Clin. Endocrinol. Metab., May 1, 2005; 90(5): 2982 - 2987. [Abstract] [Full Text] [PDF]

				J. D. Veldhuis, J. Frystyk, A. Iranmanesh, and H. Orskov Testosterone and Estradiol Regulate Free Insulin-Like Growth Factor I (IGF-I), IGF Binding Protein 1 (IGFBP-1), and Dimeric IGF-I/IGFBP-1 Concentrations J. Clin. Endocrinol. Metab., May 1, 2005; 90(5): 2941 - 2947. [Abstract] [Full Text] [PDF]

				J. D. Veldhuis, L. Farhy, A. L. Weltman, J. Kuipers, J. Weltman, and L. Wideman Gender Modulates Sequential Suppression and Recovery of Pulsatile Growth Hormone Secretion by Physiological Feedback Signals in Young Adults J. Clin. Endocrinol. Metab., May 1, 2005; 90(5): 2874 - 2881. [Abstract] [Full Text] [PDF]

				R. G. Smith, L. Betancourt, and Y. Sun Molecular Endocrinology and Physiology of the Aging Central Nervous System Endocr. Rev., April 1, 2005; 26(2): 203 - 250. [Abstract] [Full Text] [PDF]

				C. Soares-Welch, L. Farhy, K. L. Mielke, F. H. Mahmud, J. M. Miles, C. Y. Bowers, and J. D. Veldhuis Complementary Secretagogue Pairs Unmask Prominent Gender-Related Contrasts in Mechanisms of Growth Hormone Pulse Renewal in Young Adults J. Clin. Endocrinol. Metab., April 1, 2005; 90(4): 2225 - 2232. [Abstract] [Full Text] [PDF]

				J. D. Veldhuis, S. M. Anderson, A. Iranmanesh, and C. Y. Bowers Testosterone Blunts Feedback Inhibition of Growth Hormone Secretion by Experimentally Elevated Insulin-Like Growth Factor-I Concentrations J. Clin. Endocrinol. Metab., March 1, 2005; 90(3): 1613 - 1617. [Abstract] [Full Text] [PDF]

				M. Gola, S. Bonadonna, M. Doga, and A. Giustina Growth Hormone and Cardiovascular Risk Factors J. Clin. Endocrinol. Metab., March 1, 2005; 90(3): 1864 - 1870. [Abstract] [Full Text] [PDF]

				D. Erickson, D. M. Keenan, L. Farhy, K. Mielke, C. Y. Bowers, and J. D. Veldhuis Determinants of Dual Secretagogue Drive of Burst-Like Growth Hormone Secretion in Premenopausal Women Studied under a Selective Estradiol Clamp J. Clin. Endocrinol. Metab., March 1, 2005; 90(3): 1741 - 1751. [Abstract] [Full Text] [PDF]

				S. Bonadonna, A. Burattin, M. Nuzzo, G. Bugari, E. A. Rosei, D. Valle, N. Iori, J. P Bilezikian, J. D Veldhuis, and A. Giustina Chronic glucocorticoid treatment alters spontaneous pulsatile parathyroid hormone secretory dynamics in human subjects Eur. J. Endocrinol., February 1, 2005; 152(2): 199 - 205. [Abstract] [Full Text] [PDF]

				M. Malerba, S. Bossoni, A. Radaeli, E. Mori, S. Bonadonna, A. Giustina, and C. Tantucci Growth Hormone Response to Growth Hormone-Releasing Hormone Is Reduced in Adult Asthmatic Patients Receiving Long-term Inhaled Corticosteroid Treatment Chest, February 1, 2005; 127(2): 515 - 521. [Abstract] [Full Text] [PDF]

				M.-L. Healy, R. Dall, J. Gibney, E. Bassett, C. Ehrnborg, C. Pentecost, T. Rosen, A. Cittadini, R. C. Baxter, and P. H. Sonksen Toward the Development of a Test for Growth Hormone (GH) Abuse: A Study of Extreme Physiological Ranges of GH-Dependent Markers in 813 Elite Athletes in the Postcompetition Setting J. Clin. Endocrinol. Metab., February 1, 2005; 90(2): 641 - 649. [Abstract] [Full Text] [PDF]

				J. D. Veldhuis, J. N. Roemmich, E. J. Richmond, A. D. Rogol, J. C. Lovejoy, M. Sheffield-Moore, N. Mauras, and C. Y. Bowers Endocrine Control of Body Composition in Infancy, Childhood, and Puberty Endocr. Rev., February 1, 2005; 26(1): 114 - 146. [Abstract] [Full Text] [PDF]

				J.-W. Chen, K. Hojlund, H. Beck-Nielsen, J. Sandahl Christiansen, H. Orskov, and J. Frystyk Free Rather than Total Circulating Insulin-Like Growth Factor-I Determines the Feedback on Growth Hormone Release in Normal Subjects J. Clin. Endocrinol. Metab., January 1, 2005; 90(1): 366 - 371. [Abstract] [Full Text] [PDF]

				M. O. van Aken, A. M. Pereira, M. Frolich, J. A. Romijn, H. Pijl, J. D. Veldhuis, and F. Roelfsema Growth hormone secretion in primary adrenal Cushing's syndrome is disorderly and inversely correlated with body mass index Am J Physiol Endocrinol Metab, January 1, 2005; 288(1): E63 - E70. [Abstract] [Full Text] [PDF]

				J. D. Veldhuis, J. T. Patrie, K. T. Brill, J. Y. Weltman, E. E. Mueller, C. Y. Bowers, and A. Weltman Contributions of Gender and Systemic Estradiol and Testosterone Concentrations to Maximal Secretagogue Drive of Burst-Like Growth Hormone Secretion in Healthy Middle-Aged and Older Adults J. Clin. Endocrinol. Metab., December 1, 2004; 89(12): 6291 - 6296. [Abstract] [Full Text] [PDF]

				J. D. Veldhuis, J. T. Patrie, K. Frick, J. Y. Weltman, and A. Weltman Sustained Growth Hormone (GH) and Insulin-Like Growth Factor I Responses to Prolonged High-Dose Twice-Daily GH-Releasing Hormone Stimulation in Middle-Aged and Older Men J. Clin. Endocrinol. Metab., December 1, 2004; 89(12): 6325 - 6330. [Abstract] [Full Text] [PDF]

				C. Ameen, D. Linden, B.-M. Larsson, A. Mode, A. Holmang, and J. Oscarsson Effects of gender and GH secretory pattern on sterol regulatory element-binding protein-1c and its target genes in rat liver Am J Physiol Endocrinol Metab, December 1, 2004; 287(6): E1039 - E1048. [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]

				K.-C. Leung, G. Johannsson, G. M. Leong, and K. K. Y. Ho Estrogen Regulation of Growth Hormone Action Endocr. Rev., October 1, 2004; 25(5): 693 - 721. [Abstract] [Full Text] [PDF]

				A. C. Gore, B. M. Windsor-Engnell, and E. Terasawa Menopausal Increases in Pulsatile Gonadotropin-Releasing Hormone Release in a Nonhuman Primate (Macaca mulatta) Endocrinology, October 1, 2004; 145(10): 4653 - 4659. [Abstract] [Full Text] [PDF]