HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 291/6/E1290    most recent 00201.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Alba, M. Articles by Salvatori, R. Search for Related Content PubMed PubMed Citation Articles by Alba, M. Articles by Salvatori, R.

Once-daily administration of CJC-1295, a long-acting growth hormone-releasing hormone (GHRH) analog, normalizes growth in the GHRH knockout mouse

¹Department of Medicine, Division of Endocrinology, Johns Hopkins University School of Medicine, Baltimore, Maryland; ²Conjuchem, Incorporated, Montreal, Quebec, Canada; ³Department of Medicine, Section of Endocrinology, University of Illinois at Chicago, Chicago, Illinois

Submitted 26 April 2006 ; accepted in final form 29 June 2006

Although the majority of children with isolated growth hormone (GH) deficiency have a good growth response to GH-releasing hormone (GHRH), the use of this therapeutic agent is limited by its very short half-life. Indeed, we have shown that, in mice with GHRH gene ablation (GHRH knockout; GHRHKO), even twice-daily injections of a GHRH analog are unable to normalize growth. CJC-1295 is a synthetic GHRH analog that selectively and covalently binds to endogenous albumin after injection, thereby extending its half-life and duration of action. We report the effects of CJC-1295 administration in GHRHKO animals. Three groups of 1-wk-old GHRHKO mice were treated for 5 wk with 2 µg of CJC-1295 at intervals of 24, 48, and 72 h. Placebo-treated GHRHKO mice and mice heterozygous for the GHRHKO allele served as controls. GHRHKO animals receiving daily doses of CJC-1295 exhibited normal body weight and length. Mice treated every 48 and 72 h reached higher body weight and length than placebo-treated animals, without full growth normalization. Femur and tibia length remained normal in animals treated every 24 and 48 h. Relative lean mass and subcutaneous fat mass were normal in all treated groups. CJC-1295 caused an increase in total pituitary RNA and GH mRNA, suggesting that proliferation of somatotroph cells had occurred, as confirmed by immunohistochemistry images. These findings demonstrate that treatment with once-daily administration of CJC-1295 is able to maintain normal body composition and growth in GHRHKO mice. The same dose is less effective when administered every 48 or 72 h.

growth hormone deficiency; growth hormone-releasing hormone therapy; growth hormone-releasing hormone knockout mice

This article has been cited by other articles:

				M. G.-S. Frutos, L. Cacicedo, C. Fernandez, D. Vicent, B. Velasco, H. Zapatero, and F. Sanchez-Franco Insights into a role of GH secretagogues in reversing the age-related decline in the GH/IGF-I axis Am J Physiol Endocrinol Metab, November 1, 2007; 293(5): E1140 - E1152. [Abstract] [Full Text] [PDF]