Study summary · research use only
Once-daily administration of CJC-1295, a long-acting growth hormone-releasing hormone (GHRH) analog, normalizes growth in the GHRH knockout mouse
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
In this mouse study, the authors examined the long-acting GHRH analog CJC-1295 in GHRH-knockout (GHRHKO) mice, which have growth deficiency. Three groups of 1-week-old GHRHKO mice received 2 microg of CJC-1295 every 24, 48, or 72 h for 5 weeks, with placebo-treated GHRHKO and heterozygous mice as controls. They report that daily CJC-1295 produced normal body weight and length, while 48- and 72-h intervals gave higher weight and length than placebo without full normalization; femur and tibia length remained normal with 24- and 48-h dosing. CJC-1295 increased total pituitary RNA and GH mRNA, suggesting somatotroph proliferation. The authors conclude once-daily CJC-1295 maintained normal growth in these mice.
Abstract
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.
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