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 production of insulin-like growth factor-I (IGF-I) by thyroid follicular cells (TFCs) in vitro has been investigated as a possible mechanism underlying the iodide-dependent control of TFC proliferation, IGF-I release from primary monolayer cultures of porcine TFCs increased 5-fold between 24 and 168 h of incubation, Confirmation of a mediating role of IGF-I in TFC proliferation was obtained by exposing TFCs to an immunoadsorbing IGF-I antiserum, which led to a significant (P < 0.05) decline in [methyl-H-3] thymidine incorporation, relative to TFCs exposed to preimmune 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 medium, This was accompanied by a reduction in [methyl-H-3] thymidine incorporation that was affected by ICE-I immunoneutralization. The inhibitory effect of NaI on IGF-I production and [methyl-H-3]thymidine incorporation were reversed by the thionamide compound methinazole (MMI; 1 mmol/l), exposure to which also led to significant (P < 0.001) increases above control values, However, a residual suppressive effect of NaI on [methyl-H-3]thymidine incorporation suggested that certain of the TFC growth-attenuating effects of iodide may not be dependent upon organification. While providing evidence, therefore, for a direct relationship between iodide exposure, suppression of autocrine IGF-I production and a regulation of TFC proliferation, the present studies also suggest that suppression of TFC proliferation by iodide may be partially mediated by MMI-insensitive events.