Effects of transforming growth factor-beta on deoxyribonucleic acid synthesis and iodine metabolism in porcine thyroid cells in culture.
The effect of transforming growth factor (TGF)-beta on DNA synthesis and iodine metabolism was studied in cultured porcine thyroid cells. TGF-beta dose-dependently inhibited DNA synthesis stimulated by both insulin-like growth factor I and epidermal growth factor but did not affect the number or affinity of receptors for the two growth factors, suggesting that TGF-beta inhibits postreceptor events responsible for initiation of DNA synthesis. TGF-beta was a potent inhibitor of iodine metabolism. When porcine thyroid cells were cultured with TSH for 3 days in the presence of TGF-beta, TSH-induced iodide uptake and organification were reduced at rates that were dependent on the TGF-beta concentrations. The inhibition was detectable at TGF-beta concentrations as low as 50 pg/ml, and complete suppression was seen at 1 ng/ml. Only 6 h of exposure to TGF-beta resulted in a significant inhibition of TSH-induced iodine metabolism. Treatment of thyroid cells with TGF-beta for 3 days did not reduce cAMP production stimulated by TSH. Moreover, the intracellular cAMP level of thyroid cells cultured with TSH plus TGF-beta did not differ from that of cells cultured with TSH alone. TGF-beta decreased iodide uptake stimulated by forskolin or 8-bromo-cAMP. These results strongly suggest that TGF-beta inhibits TSH-stimulated iodine metabolism, at least in part, by affecting events subsequent to cAMP production. The physiological role of TGF-beta remains to be determined, but it may be involved in the regulation of thyroid cell growth and function.
Tsushima
T
T
Department of Medicine 2, Tokyo Women's Medical College, Japan.
Arai
M
M
Saji
M
M
Ohba
Y
Y
Murakami
H
H
Ohmura
E
E
Sato
K
K
Shizume
K
K
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D004247:DNA / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007454:Iodides / Q000378:metabolism; D007455:Iodine / Q000378:metabolism*; D007457:Iodine Radioisotopes; D010455:Peptides / Q000494:pharmacology*; D013552:Swine; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism*; D013972:Thyrotropin / Q000494:pharmacology; D015291:Transforming Growth Factors
D007454:Iodides; D007457:Iodine Radioisotopes; D010455:Peptides; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; D015291:Transforming Growth Factors; D013972:Thyrotropin; D004247:DNA; D007455:Iodine; D000242:Cyclic AMP