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Iodine inhibits the proliferation of rat thyroid cells in culture
D Tramontano1, B M Veneziani, A Lombardi
1Charles A. Dana Research Institute, Department of Medicine, Beth Israel Hospital, Boston, Massachusetts.
Abstract:
We have explored the mechanisms whereby iodine inhibits thyroid growth using as models both the FRTL5 line of rat thyroid follicular cells that require TSH for growth and the M12 line of mutant cells that grow in the absence of TSH. Between 0.01-1.0 mM, NaI produced a dose-dependent inhibition of TSH stimulation of [3H]thymidine incorporation and replication in FRTL5 cells as well as spontaneous growth in M12 cells. Iodide also inhibited the cAMP-dependent growth of FRTL5 cells induced by forskolin and (Bu)2cAMP, as well as the cAMP-independent mitogenesis induced by insulin-like growth factor-I. The effect of iodide to inhibit both TSH- and insulin-like growth factor-I-stimulated growth in FRTL5 cells was abolished by concomitant culture with methimazole, and no iodide inhibition of growth was observed in L6 myoblasts and BRL 30E hepatocytes. Exposure of cells to iodide under conditions that resulted in inhibition of TSH-stimulated growth did not significantly alter the ability of TSH to increase the intracellular cAMP concentration, nor did iodide alter two responses to TSH in FRTL5 cells that depend upon an increase in cAMP concentration: down-regulation of TSH receptor and cytoskeletal reorganization. We conclude that iodide exerts its inhibitory action on the growth of thyroid cells at multiple loci related to both the cAMP-dependent and cAMP-independent pathways of mitogenic regulation.
Insights
Iodine (NaI) inhibits thyroid cell growth by affecting multiple pathways. This study shows iodide impacts both thyroid-stimulating hormone (TSH) dependent and independent growth mechanisms.
Area of Science:
- Endocrinology
- Cell Biology
- Molecular Biology
Background:
- Thyroid growth is regulated by thyroid-stimulating hormone (TSH).
- Iodine is essential for thyroid hormone synthesis but its role in thyroid growth is complex.
- Understanding iodine's effects on thyroid cell proliferation is crucial for managing thyroid disorders.
Purpose of the Study:
- To investigate the mechanisms by which iodine (NaI) inhibits thyroid cell growth.
- To determine if iodide affects TSH-dependent and/or TSH-independent growth pathways.
- To identify the specific molecular targets of iodide's inhibitory action.
Main Methods:
- Utilized FRTL5 (rat thyroid follicular cells) and M12 (mutant cells) cell lines.
- Administered varying concentrations of NaI to assess dose-dependent effects on cell proliferation.
- Measured [3H]thymidine incorporation and cell replication rates.
- Investigated effects on cAMP-dependent and independent growth pathways stimulated by forskolin, (Bu)2cAMP, and insulin-like growth factor-I.
- Assessed the impact of methimazole on iodide's inhibitory effects.
- Examined TSH-induced changes in cAMP levels, TSH receptor down-regulation, and cytoskeletal reorganization.
Main Results:
- NaI demonstrated a dose-dependent inhibition of TSH-stimulated [3H]thymidine incorporation and replication in FRTL5 cells.
- Iodide also inhibited spontaneous growth in M12 cells and cAMP-dependent/independent growth in FRTL5 cells.
- Inhibition was specific to thyroid cells, as no effect was observed in L6 myoblasts or BRL 30E hepatocytes.
- Iodide's inhibitory effect was abolished by methimazole.
- Exposure to iodide did not significantly alter TSH-induced increases in intracellular cAMP or subsequent TSH responses.
Conclusions:
- Iodide inhibits thyroid cell growth through multiple mechanisms.
- These mechanisms involve both cAMP-dependent and cAMP-independent mitogenic regulatory pathways.
- Iodide's action appears to be localized downstream of cAMP generation in response to TSH.