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-3H]thymidine incorporation, relative to TFCs exposed to preimmune serum. Exposure of TFCs to sodium iodide (NaI; 0.1-100 mumol/l) led to an attenuation of the IGF-I content of the cell-conditioned medium. This was accompanied by a reduction in [methyl-3H]thymidine incorporation that was affected by IGF-I immunoneutralization. The inhibitory effect of NaI on IGF-I production and [methyl-3H]thymidine incorporation were reversed by the thionamide compound methimazole (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-3H]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.
Beere
H M
HM
School of Biological Sciences, University of Manchester, UK.
Cowin
A J
AJ
Soden
J
J
Bidey
S P
SP
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D013956:Antithyroid Agents / Q000494:pharmacology; D002455:Cell Division; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D004247:DNA / Q000096:biosynthesis; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis* / Q000276:immunology / Q000378:metabolism; D007700:Kinetics; D008713:Methimazole / Q000494:pharmacology*; D012974:Sodium Iodide / Q000494:pharmacology*; D013552:Swine; D013936:Thymidine / Q000378:metabolism; D013961:Thyroid Gland / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
D000906:Antibodies; D013956:Antithyroid Agents; D017077:Culture Media, Conditioned; D008713:Methimazole; D007334:Insulin-Like Growth Factor I; D004247:DNA; D012974:Sodium Iodide; D013936:Thymidine