IODIDE-DEPENDENT REGULATION OF THYROID FOLLICULAR CELL-PROLIFERATION - A MEDIATING ROLE OF AUTOCRINE INSULIN-LIKE GROWTH-FACTOR-I

An inhibitory action of intracellular iodide on the autocrine producti on of insulin-like growth factor-I (IGF-I) by thyroid follicular cells (TFCs) in vitro has been investigated as a possible mechanism underly ing the iodide-dependent control of TFC proliferation, IGF-I release f rom primary monolayer cultures of porcine TFCs increased 5-fold betwee n 24 and 168 h of incubation, Confirmation of a mediating role of IGF- I in TFC proliferation was obtained by exposing TFCs to an immunoadsor bing IGF-I antiserum, which led to a significant (P < 0.05) decline in [methyl-H-3] thymidine incorporation, relative to TFCs exposed to pre immune serum, Exposure of TFCS to sodium iodide (NaI; 0.1-100 mu mol/l ) led to an attenuation of the IGF-I content of the cell-conditioned m edium, This was accompanied by a reduction in [methyl-H-3] thymidine i ncorporation that was affected by ICE-I immunoneutralization. The inhi bitory effect of NaI on IGF-I production and [methyl-H-3]thymidine inc orporation were reversed by the thionamide compound methinazole (MMI; 1 mmol/l), exposure to which also led to significant (P < 0.001) incre ases above control values, However, a residual suppressive effect of N aI on [methyl-H-3]thymidine incorporation suggested that certain of th e TFC growth-attenuating effects of iodide may not be dependent upon o rganification. While providing evidence, therefore, for a direct relat ionship between iodide exposure, suppression of autocrine IGF-I produc tion and a regulation of TFC proliferation, the present studies also s uggest that suppression of TFC proliferation by iodide may be partiall y mediated by MMI-insensitive events.