Roles of growth hormone in liver growth and mesenchymal stem cell myogenic and adipogenic lineage commitment

Growth hormone (GH) has growth-stimulating effects on skeletal muscle and liver but a growth-inhibitory effect on adipose tissue. The mechanisms underlying these actions of GH are not fully understood. Two studies were conducted to achieve the following objectives: 1) to determine the cellular mechanism by which GH stimulates liver growth; 2) to determine the effects of GH on the commitment of mesenchymal stem cells (MSCs) to myogenic and adipogenic lineages. In the first study, the GH-deficient lit/lit male mice were injected (s.c.) daily with rbGH or vehicle for two weeks. GH-injected lit/lit mice tended to have a greater liver/body weight percentage than lit/lit control mice. GH injection did not alter the percentage of proliferating cells in the liver. However, GH-injected lit/lit mice had 18% larger hepatocytes and 16% less DNA per unit liver weight than those of lit/lit control mice. These data together indicate that GH stimulates liver growth in mice by increasing the size, not by increasing the number of hepatocytes. In the second study, we treated the MSC cell line C3H10T1/2 cells with or without 5'-azacytidine and rbGH for 4 days. We assessed the myogenic or adipogenic potential by determining the ability of these cells to differentiate into myotubes or adipocytes, respectively. C3H10T1/2 cells treated with 5'-azacytidine and GH formed more myotubes, myoblasts, and fewer adipocytes compared to cells treated with 5'-azacytidine alone. Taken together, these results suggest that GH enhances 5'-azacytidine-induced myogenic commitment but inhibits 5'-azacytidine-induced adipogenic commitment in C3H10T1/2 cells.