Effects of transforming growth factor alpha (TGF-alpha) on DNA synthesis and thyrotropin-induced iodine metabolism in cultured porcine thyroid cells.
Transforming growth factor alpha (TGF-alpha) is a potent mitogen that is similar structurally to epidermal growth factor (EGF). As EGF is a potent growth stimulator and an inhibitor of iodine metabolism in cultured thyroid cells of several species, we studied whether TGF-alpha has similar effects using porcine thyroid cells in culture. Recombinant human TGF-alpha dose-dependently stimulated DNA synthesis of thyroid cells, with maximal stimulation (eight- to ninefold above basal) occurring at 2 nmol/l. The potency was approximately 50% that of mouse EGF and correlated with the ability to compete with EGF for receptor binding, suggesting that the action of TGF-alpha is mediated by interaction with EGF receptors. When thyroid cells were cultured for 3 days with thyrotropin (TSH) in the presence of TGF-alpha, TSH-induced iodide uptake was inhibited in a dose-dependent manner. The potency of TGF-alpha again was approximately 50% that of EGF. Transforming growth factor alpha did not inhibit TSH-stimulated cAMP production. Moreover, iodide uptake stimulated by either forskolin or 8-bromo-cAMP also was inhibited by TGF-alpha. Thus, we conclude that TGF-alpha inhibits TSH-induced iodine metabolism largely by acting at the steps distal to cAMP production. Northern blot analysis revealed expression of TGF-alpha mRNA in porcine thyroid cells. These observations suggest that TGF-alpha acts as an autocrine modulator of growth and differentiated functions in porcine thyroid cells.
Institute for Growth Science, Tokyo, Japan.
M
M
Arai
T
T
Tsushima
O
O
Isozaki
H
H
Demura
K
K
Shizume
N
N
Emoto
M
M
Miyakawa
Y
Y
Nozoe
H
H
Murakami
E
E
Ohmura
D000818:Animals; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D004261:DNA Replication / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000494:pharmacology; D006801:Humans; D007455:Iodine / Q000378:metabolism*; D051379:Mice; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D015290:Second Messenger Systems; D013552:Swine; D013961:Thyroid Gland / Q000378:metabolism*; D013972:Thyrotropin / Q000494:pharmacology*; D013997:Time Factors; D016211:Transforming Growth Factor alpha / Q000378:metabolism / Q000494:pharmacology*
D012333:RNA, Messenger; D011994:Recombinant Proteins; D016211:Transforming Growth Factor alpha; D004815:Epidermal Growth Factor; D013972:Thyrotropin; D007455:Iodine