Growth hormone (GH) retardation of muscle damage due to immobilization in old rats. Possible intervention with a new long-acting recombinant GH.
Four weeks immobilization of the right leg of aged rats (26 months old) caused a marked 31% and 27% reduction of muscle mass of the plantaris and soleus muscles, respectively. In animals treated with 0.6 mg/kg body weight of growth hormone (GH), the reduction of weight of the above muscles was only 14.7 and 16.1%, respectively. Biochemical studies of the level of acid phosphatase as a marker of muscle catabolism showed a significant increase of this enzyme in the immobilized muscles. GH treatment had a positive effect in curtailing the increase due to immobilization. Studies on muscle protein oxidation used as another measure of damage in immobilized animals, showed a 400% increase in protein carbonyls in plantaris muscles. GH administration reduced this value significantly. One major issue hampering the clinical use of human GH (hGH) is its short half-life in vivo (14 min). In a previous work it was possible to enhance the in vivo longevity of other hormones such as follicle-stimulating hormone (FSH) and human chorionic gonadotropin (hCG) by fusing carboxyl-terminal peptide (CTP) of the hCG gene to the above hormones. The CTP has four serine-linked oligosaccharides, which have been shown to be important in maintaining the longer half-lives of these hormones. With the above rationale of using the CTP as a general target to increase the potency of bioactive hormones, we have now fused the CTP with hGH. This has provided us with a new successfully constructed recombinant hGH, which is currently being tested for its biological potency and for possible use in aging animals.
Fares
F A
FA
Department of Biochemistry, Carmel Medical Center, Haifa, Israel.
Gruener
N
N
Carmeli
E
E
Reznick
A Z
AZ
D000375:Aging / Q000473:pathology*; D000818:Animals; D005260:Female; D013006:Growth Hormone / Q000378:metabolism*; D006614:Hindlimb / Q000473:pathology*; D007103:Immobilization; D018482:Muscle, Skeletal / Q000378:metabolism; D009132:Muscles / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D011995:Recombination, Genetic
D013006:Growth Hormone