Comparison of Bone Changes between Neonatally Monosodium Glutamate-Treated Rats and Mini Rats.

Abstract

Growth hormone (GH) plays an important role in longitudinal bone growth, and hypophysectomized rats or mutant rats exhibiting dwarfism have generally been used as a GH-deficient model for humans. There also has been a GH deficient model produced by subcutaneous administration to neonatal rats with monosodium glutamate (MSG), followed by destroying GH releasing hormone (GHRH) neurons in the hypothalamic arcuate nucleus, leading to a reduction of GHRH release and a resultant reduction of GH. Recently, Mini rats, a Wistar-derived transgenic rat strain harboring a rat GH antisense gene and showing 40% lower plasma GH levels than Wistar rats, have been developed. In a previous study, Mini rats showed a smaller femur size with lower mineral density and a reduction of the metaphyseal and diaphyseal bone mass. In the present study, neonates of Wistar rats were treated subcutaneously with MSG to obtain GH-deficient rats (MSG rats), and their bones were examined and compared with age-matched MSG-untreated Wistar rats and Mini rats. Compared with the Wistar rats, body weights of the MSG rats were comparable, whereas those of the Mini rats were significantly lower. Bone size, bone mineral content and mineral density were significantly lower in the MSG rats and Mini rats than those in the Wistar rats. Histologically, the amounts of the metaphyseal cancellous bone mass and diaphyseal cortical bone mass were less in the MSG rats and much less in the Mini rats. Compared with the Wistar rats, the growth plate width and longitudinal growth rate were similarly lower. However, there were no differences in bone surface-referent parameters in the secondary spongiosa for histomorphometry among the MSG rats, Wistar rats, and Mini rats, indicating that GH may not influence bone remodeling. Thus, Mini rats are considered to be a useful model for clarifying features of GH-deficiency and examining the effects of various treatments on the bone without any specific surgery or drug administration.