Suppression of Rat Thyrotroph and Thyroid Cell Function by Tumor Necrosis Factor-α

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Abstract
We studied the effect of tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), and interferon-γ (IFN-γ) on the function of thyroid cells and pituitary thyrotrophs. In FRTL-5 rat thyroid cells, both human and murine TNF-α inhibited basal and TSH-stimulated [l25I]iodide transport. IL-1 shared this action with TNF-α, but was less potent. IL-1 and IFN-γ did not cause a further reduction of TNF-γ-induced inhibition of [125I]iodide transport. TNF-α, 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-α 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-α action, suggesting that the mechanism of TNF-α action on thyroid cells is independent of protein kinase A and C. In pituitary cells, both human and murine TNF-α did not affect basal TSH secretion, but TNF-α reduced TRH-stimulated TSH secretion. This study provides further in vitro evidence that TNF-α inhibits the function of the hypothalamus—pituitary—thyroid axis acting directly on both the pituitary and thyroid glands.