Dedifferentiation of cultured thyroid cells by epidermal growth factor: some insights into the mechanism.
Epidermal growth factor (EGF) has been shown to enhance both the proliferation and dedifferentiation of thyroid cells in culture, leading to a maintained dedifferentiated state, even in the presence of thyrotropin (TSH). Since this maintained loss of differentiated function is not seen with other mitogens, it may relate to a regulatory role for EGF in thyroid function. Therefore, we have examined the loci affected by the dedifferentiative actions of EGF using porcine thyroid cells in culture. EGF (10 ng/ml) induces a loss of thyrotropin (TSH) receptors with a time course identical to the loss in ability to transport iodide. This could account for the difference in extent of iodide uptake and morphological dedifferentiation seen between TSH- and cAMP-supported cells, although the fact that cAMP-supported cells also dedifferentiate implies a lesion distal to the cyclase. Reciprocal plot analysis of iodide uptake in control and EGF-treated cells shows that EGF increases the Km for iodide transport, corresponding to a decreased affinity of iodide pump sites for iodide. These effects on iodide pump affinity and TSH receptor number may result from reversal of thyroid cell polarity in monolayer culture, or they may be the result of more specific actions of EGF at these loci. It has been possible to discriminate between the proliferative and dedifferentiating actions of EGF using amiloride, a non-specific inhibitor of the Na+/H+ antiporter. An optimum concentration of amiloride (0.1 mM) was able to block EGF-stimulated incorporation of [3H]thymidine into DNA without preventing the blockade of iodide uptake, which implies that dedifferentiation is not a consequence of proliferation.(ABSTRACT TRUNCATED AT 250 WORDS)
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D000242:Cyclic AMP / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D007454:Iodides / Q000378:metabolism; D007700:Kinetics; D011989:Receptors, Thyrotropin / Q000378:metabolism; D013552:Swine; D013961:Thyroid Gland / Q000166:cytology* / Q000378:metabolism; D013972:Thyrotropin / Q000378:metabolism / Q000494:pharmacology
D007454:Iodides; D011989:Receptors, Thyrotropin; D004815:Epidermal Growth Factor; D000584:Amiloride; D013972:Thyrotropin; D000242:Cyclic AMP