Growth hormone action on bone is partially independent of hepatic IGF-1 production

Growth hormone (GH) plays an important role in regulating bone formation during growth. Although GH can bind its own receptor, it also stimulates the synthesis of insulin-like growth factor I (IGF-I). Hepatic synthesis accounts for most of circulating IGF-1, which acts as a hormone to regulate different processes.

IGF-1 invalidation in mice results in reduced bone size and bone mineral density. Liver-specific IGF-1 invalidation in mice, which reduced circulating IGF-I by 75%, leads to a reduction of cortical bone thickness without affecting bone size. Mice with liver specific IGF-I invalidation (LID mice) have a threefold increase in GH circulating concentration. The putative compensatory role of GH in absence of IGF-1 hepatic synthesis has not been studied.

Courtland and colleagues [1] recently assessed this question using pegvisomant, a specific inhibitor of the GH receptor. LID and control mice were treated with either pegvisomant or vehicle from 4 to 8 weeks of age. As expected, pegvisomant treatment effectively blocked GH signaling in the liver. It also reduced serum IGF-1 concentration, body weight, femoral length, and lean mass in both control and LID mice. It also raised fat mass in both strains. Pegvisomant reduced mean cortical bone traits in both control and LID mice. Remarkably, pegvisomant treated mice were statistically indistinguishable from vehicle treated LID mice when considering the cortical bones parameters. Mechanical bone properties were affected by pegvisomant in both strains. Histomorphometric analysis revealed that pegvisomant treatment reduced bone formation rate in both strains but exclusively at the periosteal surface.

Thus, GH action on bone appears to be partially independent of hepatic IGF-1 production.

1. Courtland HW et al. J Bone Miner Res. 2011;26:761-768.