Effects of Growth Hormone on Bone in Mini Rats

Abstract

Mini rats have been reported to be a Wistar-derived strain of transgenic rats that harbors a rat growth hormone (GH) antisense gene and shows lower plasma GH levels than Wistar rats. Our previous study has revealed that: 1) Mini rats show smaller hind limbs with lower metaphyseal and diaphyseal bone mass than Wistar rats; 2) that the differences of the diaphyseal cortical bone mass and metaphyseal bone mass between Mini rats and Wistar rats are due largely to the differences in the periosteal bone formation and longitudinal growth rate, respectively, and ; 3) that the bone turnover in the secondary spongiosa, an area were bone remodeling may occur, does not differ between the two strains. In the present study, 8-week-old male Mini rats were treated intraperitoneally with GH at doses of 0, 2, 6 or 20 IU/kg/time twice daily for 14 days. After the dosage period, we measured the size, bone mineral content, and mineral density of the femur and tibia in each group, and we performed cancellous and cortical bone histomorphometry on the tibia to examine the effects of GH on the bone modeling and remodeling. In the GH-treated groups there were increases in the metaphyseal cancellous bone mass, growth plate width, longitudinal growth rate, and periosteal bone formation accompanied by increases in bone size, mineral content, and mineral density in a dose-related fashion. However, bone histomorphometric parameters related to bone turnover in the secondary spongiosa of the metaphysis, where lamellar bone formation took place, did not differ between the control and GH-treated groups. These findings indicated that GH may not influence bone remodeling in the latter groups, and that GH replacement may not influence the number of osteoclasts involved in bone resorption in Mini rats as a whole.