EFFECTS OF INSULIN-LIKE GROWTH-FACTOR-I ON GROWTH, EPITHELIAL BARRIERAND IODIDE TRANSPORT IN POLARIZED PIG THYROCYTE MONOLAYERS

The effects of insulin-like growth factor I (IGF-I) on mitogenesis, ep ithelial barrier function and transepithelial iodide transport were st udied in confluent. polarized monolayers of pig thyrocytes cultured on filter in Transwell bicameral chambers. The growth rate in controls c ultured in 1% fetal calf serum was low, Insulin-like growth factor I s timulated dose-dependently the incorporation of [H-3]thymidine, maxima lly at 100 ng/ml, which corresponded to an increase of DNA content by 60% after 6 days. Thyrotropin (1 mU/ml) alone did not stimulate cell m ultiplication but inhibited partially the stimulatory effect of IGF-I. Insulin-like growth factor I (100 ng/ml) increased within 10 min the transepithelial potential difference, which remained elevated for seve ral days, but did not significantly change the transepithelial resista nce. When added together, IGF-I reinforced the effects of TSH on poten tial difference (increase) and resistance (decrease), A preserved epit helial barrier in IGF-T-treated cultures was confirmed by observing a normal immunolocalization of the tight junction protein ZO-1 and an un changed ultrastructure of the junctional complex, Insulin-like growth factor I increased the transepithelial flux of I-125(-) in the basal-t o-apical, but not in the opposite, direction. Stimulation of iodide tr ansport by IGF-I was modest after 2 days and pronounced after 6 days. In comparison, TSH-stimulated iodide transport was higher after 2 days but lower after 6 days, Both TSH and IGF-I were strongly synergistic, after 6 days amounting to a 90-fold increase over the control basoapi cal I-125(-) transfer. The simultaneous accumulation of I-125(-) in th e cell layer was increased two- to fourfold by IGF-I and/or TSH. In co nclusion, IGF-I is able to induce growth in preformed monolayers of pi g thyrocytes cultured on permeable filter. During these conditions, th e mitogenic effect of IGF-I is partially inhibited by TSH, which has n o growth-promoting action on its own, The transepithelial transport of iodide and bulk electrolytes is altered by IGF-I without affecting th e epithelial barrier function. Specifically, IGF-I up-regulates the ac tivity of the basolateral iodide pump and increases the iodide permeab ility of the apical plasma membrane. The action of ICE-I on iodide tra nsport is independent of, although synergistic with, that of TSH, The findings support the notion that IGF-I may be an important regulator o f thyroid growth and differentiated functions.