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 Maheshwari, H. G. Articles by Baumann, G. Search for Related Content PubMed PubMed Citation Articles by Maheshwari, H. G. Articles by Baumann, G.

Selective Lack of Growth Hormone (GH) Response to the GH-Releasing Peptide Hexarelin in Patients with GH-Releasing Hormone Receptor Deficiency¹

Center for Endocrinology, Metabolism, and Molecular Medicine, Department of Medicine, Northwestern University Medical School (H.G.M., G.B.), Chicago, Illinois 60611; and the Department of Endocrinology, Christie Hospital (A.R., S.M.S.), Withington, Manchester, United Kingdom M20 4BX

Address all correspondence and requests for reprints to: G. Baumann, M.D., Northwestern University Medical School, 303 East Chicago Avenue, Chicago, Illinois 60611. E-mail: gbaumann{at}nwu.edu

The mechanism of the synergistic relationship between GH-releasing peptide (GHRP) and GHRH with respect to GH secretion is poorly understood. We report the response to hexarelin, a potent GHRP, in patients affected with a homozygous mutation in the GHRH receptor gene, with consequent GHRH resistance and GH-deficient dwarfism. This newly described syndrome is the human homolog of the little (lit/lit) mouse. Intravenous administration of hexarelin (2 µg/kg) to four male adult patients (dwarfs of Sindh) resulted in a complete lack of elevation in plasma GH levels (<1 ng/mL), an at least 50- to 100-fold deviation from the normal response. In contrast, plasma PRL, ACTH, and cortisol levels rose in a normal manner in response to hexarelin. We conclude that an intact GHRH signaling system is critical for GHRPs to exert their effect on GH release, but that the GHRH system is not necessary for the effect of GHRP on PRL and ACTH secretion. Hexarelin (and probably other GHRPs) are not effective agents for the treatment of patients with GHRH resistance due to GHRH receptor deficiency.

This article has been cited by other articles:

				F. F. Casanueva, J. P. Camina, M. C. Carreira, Y. Pazos, J. L. Varga, and A. V. Schally Growth hormone-releasing hormone as an agonist of the ghrelin receptor GHS-R1a PNAS, December 23, 2008; 105(51): 20452 - 20457. [Abstract] [Full Text] [PDF]

				M. Maghnie, M. C. Pennati, E. Civardi, N. Di Iorgi, G. Aimaretti, M. L. Foschini, G. Corneli, C. Tinelli, E. Ghigo, R. Lorini, et al. GH response to ghrelin in subjects with congenital GH deficiency: evidence that ghrelin action requires hypothalamic-pituitary connections Eur. J. Endocrinol., April 1, 2007; 156(4): 449 - 454. [Abstract] [Full Text] [PDF]

				D. Stevanovic, V. Milosevic, D. Nesic, V. Ajdzanovic, V. Starcevic, and W. B. Severs A BRIEF COMMUNICATION: Central Effects of Ghrelin on Serum Growth Hormone and Morphology of Pituitary Somatotropes in Rats. Experimental Biology and Medicine, November 1, 2006; 231(10): 1610 - 1615. [Abstract] [Full Text] [PDF]

				C. Moore, S. Shalet, K. Manickam, T. Willard, H. Maheshwari, and G. Baumann Voice Abnormality in Adults with Congenital and Adult-Acquired Growth Hormone Deficiency J. Clin. Endocrinol. Metab., July 1, 2005; 90(7): 4128 - 4132. [Abstract] [Full Text] [PDF]

				H. Ariyasu, K. Takaya, H. Iwakura, H. Hosoda, T. Akamizu, Y. Arai, K. Kangawa, and K. Nakao Transgenic Mice Overexpressing Des-Acyl Ghrelin Show Small Phenotype Endocrinology, January 1, 2005; 146(1): 355 - 364. [Abstract] [Full Text] [PDF]

				B. Bodosi, J. Gardi, I. Hajdu, E. Szentirmai, F. Obal Jr., and J. M. Krueger Rhythms of ghrelin, leptin, and sleep in rats: effects of the normal diurnal cycle, restricted feeding, and sleep deprivation Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2004; 287(5): R1071 - R1079. [Abstract] [Full Text] [PDF]

				A. J. van der Lely, M. Tschop, M. L. Heiman, and E. Ghigo Biological, Physiological, Pathophysiological, and Pharmacological Aspects of Ghrelin Endocr. Rev., June 1, 2004; 25(3): 426 - 457. [Abstract] [Full Text] [PDF]

				S. Lall, N. Balthasar, D. Carmignac, C. Magoulas, A. Sesay, P. Houston, K. Mathers, and I. Robinson Physiological Studies of Transgenic Mice Overexpressing Growth Hormone (GH) Secretagogue Receptor 1A in GH-Releasing Hormone Neurons Endocrinology, April 1, 2004; 145(4): 1602 - 1611. [Abstract] [Full Text] [PDF]

				G. S. Tannenbaum, J. Epelbaum, and C. Y. Bowers Interrelationship between the Novel Peptide Ghrelin and Somatostatin/Growth Hormone-Releasing Hormone in Regulation of Pulsatile Growth Hormone Secretion Endocrinology, March 1, 2003; 144(3): 967 - 974. [Abstract] [Full Text] [PDF]

				F. Obal Jr., J. Alt, P. Taishi, J. Gardi, and J. M. Krueger Sleep in mice with nonfunctional growth hormone-releasing hormone receptors Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2003; 284(1): R131 - R139. [Abstract] [Full Text] [PDF]

				F. Weekers, E. Van Herck, W. Coopmans, M. Michalaki, C. Y. Bowers, J. D. Veldhuis, and G. Van den Berghe A Novel in Vivo Rabbit Model of Hypercatabolic Critical Illness Reveals a Biphasic Neuroendocrine Stress Response Endocrinology, March 1, 2002; 143(3): 764 - 774. [Abstract] [Full Text] [PDF]

				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]

				F. Roelfsema, N. R. Biermasz, R. G. Veldman, J. D. Veldhuis, M. Frolich, W. H. Stokvis-Brantsma, and J.-M. Wit Growth Hormone (GH) Secretion in Patients with an Inactivating Defect of the GH-Releasing Hormone (GHRH) Receptor Is Pulsatile: Evidence for a Role for Non-GHRH Inputs into the Generation of GH Pulses J. Clin. Endocrinol. Metab., June 1, 2001; 86(6): 2459 - 2464. [Abstract] [Full Text] [PDF]

				A. Tivesten, E. Bollano, K. Caidahl, V. Kujacic, X. Y. Sun, T. Hedner, A. Hjalmarson, B.-A. Bengtsson, and J. Isgaard The Growth Hormone Secretagogue Hexarelin Improves Cardiac Function in Rats after Experimental Myocardial Infarction Endocrinology, January 1, 2000; 141(1): 60 - 66. [Abstract] [Full Text] [PDF]

				H. G. Maheshwari, S. S. Pezzoli, A. Rahim, S. M. Shalet, M. O. Thorner, and G. Baumann Pulsatile growth hormone secretion persists in genetic growth hormone-releasing hormone resistance Am J Physiol Endocrinol Metab, April 1, 2002; 282(4): E943 - E951. [Abstract] [Full Text] [PDF]