Dedifferentiation of cultured thyroid cells by epidermal growth factor: some insights into the mechanism

Waters, M. J., Tweedale, R. C., Whip, T. A., Shaw, G., Manley, S. W. and Bourke, J. R. (1987) Dedifferentiation of cultured thyroid cells by epidermal growth factor: some insights into the mechanism. Molecular and Cellular Endocrinology, 49 2-3: 109-117. doi:10.1016/0303-7207(87)90204-8


Author Waters, M. J.
Tweedale, R. C.
Whip, T. A.
Shaw, G.
Manley, S. W.
Bourke, J. R.
Title Dedifferentiation of cultured thyroid cells by epidermal growth factor: some insights into the mechanism
Journal name Molecular and Cellular Endocrinology   Check publisher's open access policy
ISSN 0303-7207
1872-8057
Publication date 1987-02
Sub-type Article (original research)
DOI 10.1016/0303-7207(87)90204-8
Open Access Status
Volume 49
Issue 2-3
Start page 109
End page 117
Total pages 9
Place of publication Shannon, Co. Clare, Ireland
Publisher Elsevier Ireland
Language eng
Formatted abstract
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 inhibition 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.

These studies demonstrate that the dedifferentiating actions of EGF on iodide uptake can be accounted for in part by a loss of TSH receptors and a lowered iodide pump affinity. A scheme is proposed to link these actions to a possible physiological role for EGF in regulating thyroid function.
Keyword TSH receptor
Iodide pump
Amiloride
Mitogenesis
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Institute for Molecular Bioscience - Publications
 
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Created: Tue, 20 May 2014, 13:35:46 EST by Thea Monks on behalf of Institute for Molecular Bioscience