Suppression of rat thyrotroph and thyroid cell function by tumor necrosis factor-alpha.
We studied the effect of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), and interferon-gamma (IFN-gamma) on the function of thyroid cells and pituitary thyrotrophs. In FRTL-5 rat thyroid cells, both human and murine TNF-alpha inhibited basal and TSH-stimulated [125I]iodide transport. IL-1 shared this action with TNF-alpha, but was less potent. IL-1 and IFN-gamma did not cause a further reduction of TNF-alpha-induced inhibition of [125I]iodide transport. TNF-alpha, phorbol ester 12-myristate 13-acetate (PMA), and calcium ionophore (CI) A23817 all inhibited [125I]iodide transport, but high doses of PMA and CI also blocked the inhibitory action of TNF-alpha on [125I]iodide transport. Inhibition of protein kinase A and protein kinase C by H7 or HA inhibited TSH-stimulated iodide transport, but did not block the TNF-alpha action, suggesting that the mechanism of TNF-alpha action on thyroid cells is independent of protein kinase A and C. In pituitary cells, both human and murine TNF-alpha did not affect basal TSH secretion, but TNF-alpha reduced TRH-stimulated TSH secretion. This study provides further in vitro evidence that TNF-alpha inhibits the function of the hypothalamus-pituitary-thyroid axis acting directly on both the pituitary and thyroid glands.
Pang
X P
XP
Endocrine Research Laboratory, West Los Angeles Department of Veterans Affairs Medical Center, California.
Yoshimura
M
M
Hershman
J M
JM
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002460:Cell Line; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D007454:Iodides / Q000378:metabolism; D007457:Iodine Radioisotopes; D008297:Male; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013961:Thyroid Gland / Q000166:cytology / Q000502:physiology*; D013972:Thyrotropin / Q000378:metabolism / Q000494:pharmacology; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D007375:Interleukin-1; D007454:Iodides; D007457:Iodine Radioisotopes; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D000001:Calcimycin; D013973:Thyrotropin-Releasing Hormone; D007371:Interferon-gamma; D013972:Thyrotropin; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate