Medium 3,5,3'-triiodo-L-thyronine (T3) and T3 generated from L-thyroxine are exchangeable in cultured GC cells

Previous studies in rats have shown that the ratio anterior pituitary nuclear L-triiodothyronine (T3) derived from intracellular deiodination of L-thyroxine [T3(T4)]/plasma T3(T4) is much greater than for exchangeable T3 [T3(T3)]. We have addressed the hypothesis that T3(T4) is either selectively accumulated or selectively retained by nuclei in comparison to exchangeable T3 [T3(T3)] in cultured GC cells. GC cells readily generated T3 from T4. When mean medium T3(T4) was experimentally maintained at a low percentage (less than 16%) of total medium T3, to mimic in vivo conditions, nuclear T3(T4) was 2-fold greater than nuclear T3(T3) and the nuclear: medium ratio for T3(T4) was 11-13-fold greater than for T3(T3). The t1/2 of release of nuclear T3(T4) and T3(T3) were indistinguishable from one another and both sources of T3 distributed similarly between the nuclear and cytosol compartments. Thus, in agreement with previous in vivo studies, T3(T4) is derived from cellular T4 and is a significant source of nuclear T3 in GC cells. No evidence for a separate nonexchangeable T3(T4) pool was found as the almost identical cellular distribution and release rates of T3(T4) and T3(T3) from nuclei suggest that T3(T4) generated in these pituitary tumor cells is fully exchangeable. Our findings suggest that the high concentration of T3(T4) in the nuclear fraction is the result of a high intracellular production rate of T3 from T4 relative to the rate of release of T3 from the cell.