Growth hormone stimulates, through tyrosine kinase, ion transport and proliferation in human intestinal cells

Background: Growth hormone (GH) stimulates intestinal growth and differentiation and promotes water and ion absorption in the rat intestine. Epidermal growth factor has similar effects, which involve tyrosine kinase activity. The effects of growth hormone on ion transport and cell growth and the role of tyrosine kinase in these effects were examined in a human-derived intestinal cell line (Caco-2). Methods: For transport study, electrical parameters were measured in human intestinal Caco-2 cell monolayers mounted in Ussing chambers. Cell growth was monitored by counting and H-3-thymidine incorporation in the presence and absence of growth hormone. The role of tyrosine kinase was investigated by using its specific inhibitor genistein. Results: The addition of growth hormone induced a rapid, Cl--dependent, decrease in short-circuit current without affecting tissue conductance, which is consistent with an anion-absorptive effect. Incubation with growth hormone increased cell count by 85% and H-3-thymidine incorporation by 64% versus the count in control specimens. The absorptive and trophic effects of growth hormone were dose-dependent, and the maximum effective concentration was identical for each effect. Genistein blocked the growth hormone effect on ion transport and cell growth. Conclusions: Growth hormone stimulates ion absorption and cell growth in human enterocytes. Both effects result from a direct growth hormone-enterocyte interaction, and both require tyrosine kinase activity. Growth hormone may have therapeutic potential in intestinal diseases characterized by epithelial atrophy and loss of water and electrolytes.