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Physiological Reviews, Vol. 79, No. 2, April 1999, pp. 511-607
Copyright ©1999 by the American Physiological Society
Department of Pharmacology, Chemotherapy, and Toxicology, University of Milan, Milan; and Department of Biomedical and Biotechnology Sciences, University of Brescia, Brescia, Italy
Müller, Eugenio E.,
Vittorio Locatelli, and
Daniela Cocchi.
The secretion of growth
hormone (GH) is regulated through a complex neuroendocrine control
system, especially by the functional interplay of two hypothalamic
hypophysiotropic hormones, GH-releasing hormone (GHRH) and
somatostatin (SS), exerting stimulatory and inhibitory influences,
respectively, on the somatotrope. The two hypothalamic neurohormones
are subject to modulation by a host of neurotransmitters, especially
the noradrenergic and cholinergic ones and other hypothalamic
neuropeptides, and are the final mediators of metabolic, endocrine,
neural, and immune influences for the secretion of GH. Since the
identification of the GHRH peptide, recombinant DNA procedures have
been used to characterize the corresponding cDNA and to clone GHRH
receptor isoforms in rodent and human pituitaries. Parallel to research
into the effects of SS and its analogs on endocrine and exocrine
secretions, investigations into their mechanism of action have led to
the discovery of five separate SS receptor genes encoding a family of G
protein-coupled SS receptors, which are widely expressed in the
pituitary, brain, and the periphery, and to the synthesis of analogs
with subtype specificity. Better understanding of the function of GHRH,
SS, and their receptors and, hence, of neural regulation of GH
secretion in health and disease has been achieved with the discovery of a new class of fairly specific, orally active, small peptides and their
congeners, the GH-releasing peptides, acting on specific, ubiquitous seven-transmembrane domain receptors, whose natural ligands are not yet known.
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S.-G. Ren, S. Kim, J. Taylor, J. Dong, J.-P. Moreau, M. D. Culler, and S. Melmed Suppression of Rat and Human Growth Hormone and Prolactin Secretion by a Novel Somatostatin/Dopaminergic Chimeric Ligand J. Clin. Endocrinol. Metab., November 1, 2003; 88(11): 5414 - 5421. [Abstract] [Full Text] [PDF]
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J. E. Caminos, R. Nogueiras, M. Blanco, L. M. Seoane, S. Bravo, C. V. Alvarez, T. Garcia-Caballero, F. F. Casanueva, and C. Dieguez Cellular Distribution and Regulation of Ghrelin Messenger Ribonucleic Acid in the Rat Pituitary Gland Endocrinology, November 1, 2003; 144(11): 5089 - 5097. [Abstract] [Full Text] [PDF]
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D. L. Hurley, D. V. Birch, M. C. Almond, I. J. Estrada, and C. J. Phelps Reduced Hypothalamic Neuropeptide Y Expression in Growth Hormone- and Prolactin-Deficient Ames and Snell Dwarf Mice Endocrinology, November 1, 2003; 144(11): 4783 - 4789. [Abstract] [Full Text] [PDF]
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E. B. Klerman, G. K. Adler, M. Jin, A. M. Maliszewski, and E. N. Brown A statistical model of diurnal variation in human growth hormone Am J Physiol Endocrinol Metab, November 1, 2003; 285(5): E1118 - E1126. [Abstract] [Full Text] [PDF]
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L. S. Farhy and J. D. Veldhuis Joint pituitary-hypothalamic and intrahypothalamic autofeedback construct of pulsatile growth hormone secretion Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2003; 285(5): R1240 - R1249. [Abstract] [Full Text] [PDF]
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L. Liu, C. E. Dean, and T. E. Porter Thyroid Hormones Interact with Glucocorticoids to Affect Somatotroph Abundance in Chicken Embryonic Pituitary Cells in Vitro Endocrinology, September 1, 2003; 144(9): 3836 - 3841. [Abstract] [Full Text] [PDF]
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W. K. Yunker, S. Smith, C. Graves, P. J. Davis, S. Unniappan, J. E. Rivier, R. E. Peter, and J. P. Chang Endogenous Hypothalamic Somatostatins Differentially Regulate Growth Hormone Secretion from Goldfish Pituitary Somatotropes in Vitro Endocrinology, September 1, 2003; 144(9): 4031 - 4041. [Abstract] [Full Text] [PDF]
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R. Draghia-Akli, K. K. Cummings, A. S. Khan, P. A. Brown, and R. H. Carpenter Effects of plasmid-mediated growth hormone releasing hormone supplementation in young, healthy Beagle dogs J Anim Sci, September 1, 2003; 81(9): 2301 - 2310. [Abstract] [Full Text] [PDF]
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S. N. Sauter, E. Ontsouka, B. Roffler, Y. Zbinden, C. Philipona, M. Pfaffl, B. H. Breier, J. W. Blum, and H. M. Hammon Effects of dexamethasone and colostrum intake on the somatotropic axis in neonatal calves Am J Physiol Endocrinol Metab, August 1, 2003; 285(2): E252 - E261. [Abstract] [Full Text] [PDF]
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 J. Gent, M. van den Eijnden, P. van Kerkhof, and G. J. Strous Dimerization and Signal Transduction of the Growth Hormone Receptor Mol. Endocrinol., May 1, 2003; 17(5): 967 - 975. [Abstract] [Full Text] [PDF]
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 H. Hosoda, M. Kojima, T. Mizushima, S. Shimizu, and K. Kangawa Structural Divergence of Human Ghrelin. IDENTIFICATION OF MULTIPLE GHRELIN-DERIVED MOLECULES PRODUCED BY POST-TRANSLATIONAL PROCESSING J. Biol. Chem., January 3, 2003; 278(1): 64 - 70. [Abstract] [Full Text] [PDF]
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 H. Hosoda, M. Kojima, and K. Kangawa Ghrelin and the Regulation of Food Intake and Energy Balance Mol. Interv., December 1, 2002; 2(8): 494 - 503. [Abstract] [Full Text]
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 R. Xu, Y. Zhao, and C. Chen Growth hormone-releasing peptide-2 reduces inward rectifying K+ currents via a PKA-cAMP-mediated signalling pathway in ovine somatotropes J. Physiol., December 1, 2002; 545(2): 421 - 433. [Abstract] [Full Text] [PDF]
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 P. H. Lane Diabetic kidney disease: impact of puberty Am J Physiol Renal Physiol, October 1, 2002; 283(4): F589 - F600. [Abstract] [Full Text] [PDF]
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 R. Busto, A. V. Schally, J. L. Varga, M. O. Garcia-Fernandez, K. Groot, P. Armatis, and K. Szepeshazi The expression of growth hormone-releasing hormone (GHRH) and splice variants of its receptor in human gastroenteropancreatic carcinomas PNAS, September 3, 2002; 99(18): 11866 - 11871. [Abstract] [Full Text] [PDF]
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M. Gasperi, E. Cecconi, L. Grasso, L. Bartalena, R. Centoni, G. Aimaretti, F. Broglio, P. Miccoli, C. Marcocci, E. Ghigo, et al. GH Secretion Is Impaired in Patients with Primary Hyperparathyroidism J. Clin. Endocrinol. Metab., May 1, 2002; 87(5): 1961 - 1964. [Abstract] [Full Text] [PDF]
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G. Tulipano, D. Soldi, M. Bagnasco, M. D. Culler, J. E. Taylor, D. Cocchi, and A. Giustina Characterization of New Selective Somatostatin Receptor Subtype-2 (sst2) Antagonists, BIM-23627 and BIM-23454. Effects of BIM-23627 on GH Release in Anesthetized Male Rats after Short-Term High-Dose Dexamethasone Treatment Endocrinology, April 1, 2002; 143(4): 1218 - 1224. [Abstract] [Full Text] [PDF]
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P. van Kerkhof, M. Smeets, and G. J. Strous The Ubiquitin-Proteasome Pathway Regulates the Availability of the GH Receptor Endocrinology, April 1, 2002; 143(4): 1243 - 1252. [Abstract] [Full Text] [PDF]
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G. Diaz-Torga, C. Feierstein, C. Libertun, D. Gelman, M. A. Kelly, M. J. Low, M. Rubinstein, and D. Becu-Villalobos Disruption of the D2 Dopamine Receptor Alters GH and IGF-I Secretion and Causes Dwarfism in Male Mice Endocrinology, April 1, 2002; 143(4): 1270 - 1279. [Abstract] [Full Text] [PDF]
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R. Salvatori, X. Fan, P. E. Mullis, A. Haile, and M. A. Levine Decreased Expression of the GHRH Receptor Gene Due to a Mutation in a Pit-1 Binding Site Mol. Endocrinol., March 1, 2002; 16(3): 450 - 458. [Abstract] [Full Text] [PDF]
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L. S. Farhy, M. Straume, M. L. Johnson, B. Kovatchev, and J. D. Veldhuis Unequal autonegative feedback by GH models the sexual dimorphism in GH secretory dynamics Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2002; 282(3): R753 - R764. [Abstract] [Full Text] [PDF]
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M. Murata, Y. Okimura, K. Iida, M. Matsumoto, H. Sowa, H. Kaji, M. Kojima, K. Kangawa, and K. Chihara Ghrelin Modulates the Downstream Molecules of Insulin Signaling in Hepatoma Cells J. Biol. Chem., February 8, 2002; 277(7): 5667 - 5674. [Abstract] [Full Text] [PDF]
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A. Gentili, T. Mulligan, M. Godschalk, J. Clore, J. Patrie, A. Iranmanesh, and J. D. Veldhuis Unequal Impact of Short-Term Testosterone Repletion on the Somatotropic Axis of Young and Older Men J. Clin. Endocrinol. Metab., February 1, 2002; 87(2): 825 - 834. [Abstract] [Full Text] [PDF]
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J. D. Veldhuis, W. S. Evans, and C. Y. Bowers Impact of Estradiol Supplementation on Dual Peptidyl Drive of GH Secretion in Postmenopausal Women J. Clin. Endocrinol. Metab., February 1, 2002; 87(2): 859 - 866. [Abstract] [Full Text] [PDF]
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S. M. Anderson, L. Wideman, J. T. Patrie, A. Weltman, C. Y. Bowers, and J. D. Veldhuis E2 Supplementation Selectively Relieves GH's Autonegative Feedback on GH-Releasing Peptide-2-Stimulated GH Secretion J. Clin. Endocrinol. Metab., December 1, 2001; 86(12): 5904 - 5911. [Abstract] [Full Text] [PDF]
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J. Schwartz Editorial: Pulsatile Hormone Patterns Governing Transcription Factor Function Endocrinology, November 1, 2001; 142(11): 4595 - 4598. [Full Text] [PDF]
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T. C. Voss, M. P. Flynn, and D. L. Hurley IGF-I Causes an Ultrasensitive Reduction in GH mRNA Levels via an Extracellular Mechanism Involving IGF Binding Proteins Mol. Endocrinol., September 1, 2001; 15(9): 1549 - 1558. [Abstract] [Full Text] [PDF]
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F. Van Goor, Y.-X. Li, and S. S. Stojilkovic Paradoxical Role of Large-Conductance Calcium-Activated K+ (BK) Channels in Controlling Action Potential-Driven Ca2+ Entry in Anterior Pituitary Cells J. Neurosci., August 15, 2001; 21(16): 5902 - 5915. [Abstract] [Full Text] [PDF]
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M. J. Bray, T. M. Vick, N. Shah, S. M. Anderson, L. W. Rice, A. Iranmanesh, W. S. Evans, and J. D. Veldhuis Short-Term Estradiol Replacement in Postmenopausal Women Selectively Mutes Somatostatin's Dose-Dependent Inhibition of Fasting Growth Hormone Secretion J. Clin. Endocrinol. Metab., July 1, 2001; 86(7): 3143 - 3149. [Abstract] [Full Text] [PDF]
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R. G. Gondo, M. H. Aguiar-Oliveira, C. Y. Hayashida, S. P. A. Toledo, N. Abelin, M. A. Levine, C. Y. Bowers, A. H. O. Souza, R. M. C. Pereira, N. L. Santos, et al. Growth Hormone-Releasing Peptide-2 Stimulates GH Secretion in GH-Deficient Patients with Mutated GH-Releasing Hormone Receptor J. Clin. Endocrinol. Metab., July 1, 2001; 86(7): 3279 - 3283. [Abstract] [Full Text] [PDF]
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J. D. Veldhuis, M. Bidlingmaier, S. M. Anderson, Z. Wu, and C. J. Strasburger Lowering Total Plasma Insulin-Like Growth Factor I Concentrations by Way of a Novel, Potent, and Selective Growth Hormone (GH) Receptor Antagonist, Pegvisomant (B2036-Peg), Augments the Amplitude of GH Secretory Bursts and Elevates Basal/Nonpulsatile GH Release in Healthy Women and Men J. Clin. Endocrinol. Metab., July 1, 2001; 86(7): 3304 - 3310. [Abstract] [Full Text] [PDF]
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L. S. Farhy, M. Straume, M. L. Johnson, B. Kovatchev, and J. D. Veldhuis A construct of interactive feedback control of the GH axis in the male Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2001; 281(1): R38 - R51. [Abstract] [Full Text] [PDF]
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 V. ROELFSEMA and R. G. CLARK The Growth Hormone and Insulin-Like Growth Factor Axis: Its Manipulation for the Benefit of Growth Disorders in Renal Failure J. Am. Soc. Nephrol., June 1, 2001; 12(6): 1297 - 1306. [Abstract] [Full Text]
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F. Obal Jr, J. Fang, P. Taishi, B. Kacsoh, J. Gardi, and J. M. Krueger Deficiency of Growth Hormone-Releasing Hormone Signaling Is Associated with Sleep Alterations in the Dwarf Rat J. Neurosci., April 15, 2001; 21(8): 2912 - 2918. [Abstract] [Full Text] [PDF]
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