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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2006-11-3
pubmed:abstractText
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 microg 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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0193-1849
pubmed:author
pubmed:issnType
Print
pubmed:volume
291
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
E1290-4
pubmed:meshHeading
pubmed-meshheading:16822960-Aging, pubmed-meshheading:16822960-Animals, pubmed-meshheading:16822960-Blotting, Northern, pubmed-meshheading:16822960-Body Composition, pubmed-meshheading:16822960-Body Weight, pubmed-meshheading:16822960-Bone Development, pubmed-meshheading:16822960-Cell Proliferation, pubmed-meshheading:16822960-Femur, pubmed-meshheading:16822960-Growth, pubmed-meshheading:16822960-Growth Hormone, pubmed-meshheading:16822960-Growth Hormone-Releasing Hormone, pubmed-meshheading:16822960-Immunohistochemistry, pubmed-meshheading:16822960-Mice, pubmed-meshheading:16822960-Mice, Inbred C57BL, pubmed-meshheading:16822960-Mice, Knockout, pubmed-meshheading:16822960-Peptide Fragments, pubmed-meshheading:16822960-Phenotype, pubmed-meshheading:16822960-Pituitary Gland, pubmed-meshheading:16822960-Prolactin, pubmed-meshheading:16822960-RNA, Messenger, pubmed-meshheading:16822960-Tibia
pubmed:year
2006
pubmed:articleTitle
Once-daily administration of CJC-1295, a long-acting growth hormone-releasing hormone (GHRH) analog, normalizes growth in the GHRH knockout mouse.
pubmed:affiliation
Department of Medicine, Division of Endocrinology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
pubmed:publicationType
Journal Article