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Am J Physiol Endocrinol Metab 289: E762-E767, 2005. First published June 28, 2005; doi:10.1152/ajpendo.00203.2005
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Effects of long-term treatment with growth hormone-releasing peptide-2 in the GHRH knockout mouse

Maria Alba,1 Danilo Fintini,1 Cyril Y. Bowers,2 A. F. Parlow,3 and Roberto Salvatori1

1Department of Medicine, Division of Endocrinology, and the Ilyssa Center for Molecular and Cellular Endocrinology Johns Hopkins University School of Medicine, Baltimore Maryland; 2Division of Endocrinology and Metabolism, Department of Internal Medicine, Tulane University Medical Center, New Orleans, Louisiana; and 3National Hormone and Peptide Program Harbor-UCLA Medical Center, Torrance, California

Submitted 5 May 2005 ; accepted in final form 20 May 2005

Growth hormone (GH) secretagogues (GHS) stimulate GH secretion in vivo in humans and in animals. They act on the ghrelin receptor, expressed in both the hypothalamus and the pituitary. It is unknown whether GHSs act predominantly by increasing the release of hypothalamic GH-releasing hormone (GHRH) or by acting directly on the somatotroph cells. We studied whether a potent GHS could stimulate growth in the absence of endogenous GHRH. To this end, we used GHRH knockout (GHRH-KO) mice. These animals have proportionate dwarfism due to severe GH deficiency (GHD) and pituitary hypoplasia due to reduced somatotroph cell mass. We treated male GHRH-KO mice for 6 wk (from week 1 to week 7 of age) with GH-releasing peptide-2 (GHRP-2, 10 µg sc twice a day). Chronic treatment with GHRP-2 failed to stimulate somatotroph cell proliferation and GH secretion and to promote longitudinal growth. GHRP-2-treated mice showed an increase in total body weight compared with placebo-treated animals, due to worsening of the body composition alterations typical of GHD animals. These data demonstrate that GHRP-2 failed to reverse the severe GHD caused by lack of GHRH.

growth hormone-releasing hormone



Address for reprint requests and other correspondence: R. Salvatori, 1830 E. Monument St. #333, Baltimore MD 21287 (e-mail: salvator{at}jhmi.edu)




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M. Alba, D. Fintini, A. Sagazio, B. Lawrence, J.-P. Castaigne, L. A. Frohman, and R. Salvatori
Once-daily administration of CJC-1295, a long-acting growth hormone-releasing hormone (GHRH) analog, normalizes growth in the GHRH knockout mouse
Am J Physiol Endocrinol Metab, December 1, 2006; 291(6): E1290 - E1294.
[Abstract] [Full Text] [PDF]




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