THE DEGREE OF INHIBITION OF THYROID FOLLICULAR CELL-PROLIFERATION BY IODIDE IS A HIGHLY INDIVIDUAL CHARACTERISTIC OF EACH CELL AND DIFFERS PROFOUNDLY IN-VITRO AND IN-VIVO

Pharmacological concentrations of iodide (>1 x 10(-6) mol/l) are known to inhibit thyroid follicular cell growth in vitro. However, the inhibitory effect varies widely, depending on experimental conditions, and usually does not exceed 50%. We demonstrate that iodide (10(-4) mol/l) inhibits the growth of FRTL-5 cells in different passages by 11-67%. When five subclones of FRTL-5 cells were compared to the wild type, iodide-induced growth inhibition varied between 25% and 46%. The individual degree of inhibition of each clone was reproducible in two subsequent passages, suggesting that it is a stable constitutive trait. When FRTL-5 cells were grown first in three-dimensional clusters and then transplanted onto nude mice with high endogenous thyrotropin secretion, iodide at a serum concentration of less than 5.7 x 10(-7) mol/l nearly completely blocked cell replication in the transplants but not in the mice's own thyroid. Five cell lines, prepared from autonomously growing hyperthyroid feline multinodular goiters, were nearly completely resistant to the growth-inhibitory effect of iodide. These observations suggest that the sensitivity towards the growth-inhibiting effect of iodide is a highly variable, stable trait of each thyrocyte, even in cloned cell populations. Some FRTL-5 cells and, even more so, cells prepared from autonomously growing nodular feline goiters are resistant constitutively to the growth-inhibiting effect of iodide. Three-dimensional clusters of FRTL-5 cells growing as transplants in recipient mice are growth-arrested totally by iodide concentrations more than 175 times lower than those partially inhibiting monolayer cultures, while growth of the intact thyroid of the recipient mouse remains unaffected or is even enhanced. Thus, the sensitivity of thyrocytes toward iodide is different fundamentally in vitro and in vivo.