Effect of lithium on function and growth of thyroid cells in vitro.
Lithium has been reported to alter thyroid function and cause goiter in some patients. To explain the mechanism of lithium action in the thyroid gland, we studied the effect of lithium on thyroid function and cell growth in FRTL-5 rat thyroid cells and on de novo thyroid hormone formation in primary cultures of porcine thyroid follicles. TSH-induced iodide uptake was suppressed at 2 mM lithium in both FRTL-5 cells and porcine follicles. In porcine thyroid follicles, iodide uptake stimulated by 8-bromo-cAMP, iodine organification, and de novo thyroid hormone formation were also reduced by lithium; however, 2 mM lithium did not inhibit TSH-induced cAMP production. In FRTL-5 cells, lithium also inhibited forskolin-stimulated iodide uptake. These results suggested that lithium exerts its effect at a step involving cAMP signal transduction rather than inhibiting cAMP production. In both FRTL-5 thyroid cells and porcine follicles, lithium enhanced cell growth in basal states (lacking TSH) and with TSH treatment. In porcine thyroid cells, the protein kinase C activator, tetradecanoyl phorbol-13-acetate, increased cell growth, and lithium had an additive effect with tetradecanoyl phorbol-13-acetate on cell growth. To examine the possibility that the action of lithium was mediated by the protein kinase C pathway, porcine cells were incubated with lithium and H7, a selective protein kinase C inhibitor. Lithium-induced cell growth was suppressed to the basal level by H7. These results suggest that lithium exerts its growth-promoting effect through the protein kinase C system.
Urabe
M
M
Endocrine Research Laboratory, West Los Angeles Veterans Administration Medical Center, California 90073.
Hershman
J M
JM
Pang
X P
XP
Murakami
S
S
Sugawara
M
M
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D007454:Iodides / Q000378:metabolism; D007546:Isoquinolines / Q000494:pharmacology; D008094:Lithium / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D013552:Swine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013961:Thyroid Gland / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D013972:Thyrotropin / Q000494:pharmacology; D014284:Triiodothyronine / Q000502:physiology
D007454:Iodides; D007546:Isoquinolines; D010879:Piperazines; D014284:Triiodothyronine; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D013972:Thyrotropin; D008094:Lithium; D000242:Cyclic AMP; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate