SUPPRESSION OF RAT THYROTROPH AND THYROID-CELL FUNCTION BY TUMOR-NECROSIS-FACTOR-ALPHA

We studied the effect of tumor necrosis factor-alpha (TNF-alpha), inte rleukin-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 [I- 125]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 T NF-alpha-induced inhibition of [I-125]iodide transport. TNF-alpha, pho rbol ester 12-myristate 13-acetate (PMA), and calcium ionophore (CI) A 23817 all inhibited [I-125]iodide transport, but high doses of PMA and CI also blocked the inhibitory action of TNF-alpha on [I-125]iodide t ransport. Inhibition of protein kinase A and protein kinase C by H7 or HA inhibited TSH-stimulated iodide transport, but did not block the T NF-alpha action, suggesting that the mechanism of TNF-alpha action on thyroid cells is independent of protein kinase A and C. In pituitary c ells, both human and murine TNF-alpha did not affect basal TSH secreti on, but TNF-alpha reduced TRH-stimulated TSH secretion. This study pro vides further in vitro evidence that TNF-alpha inhibits the function o f the hypothalamus-pituitary-thyroid axis acting directly on both the pituitary and thyroid glands.