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 (<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 t_1/2 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.