Genetic Basis for Growth Hormone Action Identified

Researchers investigating the molecular basis for aging have found that the ability of growth hormone to increase lean body mass and bone density in the elderly and to stimulate regeneration of the liver is directly related to the activity of the Foxm1b gene.

The forkhead box (Fox) proteins, encoded by Foxm1b and related genes, are an extensive family of transcription factors that share homology in the winged helix/forkhead DNA- binding domain and play important roles in regulating cellular proliferation, differentiation, longevity, and cellular transformation.

Investigators at the University of Illinois at Chicago (USA) worked with populations of young (two-month-old) and aged (12-month-old) mice to study the effect of Foxm1b and growth hormone on liver regeneration.

They found that administration of growth hormone to aged mice whose livers had been partially removed significantly increased the activity of the Foxm1b gene. The livers of these animals regenerated at a pace similar to that of young mice. Cell proliferation peaked at just two days, and the liver was fully restored within a week. Liver regeneration in aged mice that did not receive hormone injections required a month or longer.

Growth hormone treatment of young mice that had been genetically engineered to lack the Foxm1b gene failed to restore regenerating liver cell DNA replication and mitosis caused by Foxm1b deficiency. These results, published in the December, 2003, issue of Hepatology, provided strong evidence that the presence of Foxm1b was essential for growth hormone to stimulate regenerating liver cell proliferation.

"Growth hormone levels decline as we grow older; as a result, the Foxm1b gene stops working and our bodies are less capable of repairing damage,” explained senior author Dr. Robert Costa, professor of biochemistry and molecular genetics at the University of Illinois at Chicago. "These results clearly demonstrate that Foxm1b is essential for growth hormone to spur liver regeneration.”




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University of Illinois at Chicago