Oral arginine improves linear growth of long bones and the neuroendocrine mechanism

Objective To investigate the effect of oral administration of arginine on linear growth of long bones in male pubertal rats and the underlying mechanisms, focusing on expression of genes related to the hypothalamus-pituitary growth axis and the nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) pathway. Methods Rats were randomly divided into control and intervention groups. In the intervention group, arginine was solved in water (0.045 g L -arginine was mixed with 1 mL water) and administered in rats (10 mL/kg) through gastric perfusion once per day, for totally 28 d. Rats in the control group received normal saline treatment. Bone histomorphometry analysis was used to measure growth plate width and mineral apposition rate of the tibia, as well as trabecular bone volume fraction, osteoblast surface and osteoclast surface of the femur. Serum growth hormone (GH) concentration was determined by radioimmunoassay. Real-time PCR was used to measure the expression of neuronal nitric oxide synthase ( nNOS ), soluble guanylyl cyclases ( sGCα1 and sGCβ1 ), growth hormone-releasing hormone ( Ghrh ) and somatostatin ( SS ) in hypothalamus, as well as Gh in pituitary. Western blot was used to detect the protein levels of nNOS, sGCα1 and sGCβ1 in hypothalamus. Results After treatment with arginine, the growth plate width of tibia and osteoblast surface of femur were increased ( P < 0.05), and serum GH concentration was elevated ( P < 0.05). Besides, mRNA and protein levels of nNOS and sGCα1 ( P < 0.05), as well as the expression of Gh mRNA ( P < 0.01), were significantly up-regulated, while the expression of SS mRNA was downregulated ( P < 0.05). Conclusion Oral administration of arginine could improve linear growth of long bones by regulating mRNA expression of SS and Gh and inducing GH secretion, possibly via nNOS-NO-sGC-cGMP signal transduction pathway.