EFFECTS OF INTERLEUKIN-1-BETA ON THYROTROPIN SECRETION AND THYROID-HORMONE UPTAKE IN CULTURED RAT ANTERIOR-PITUITARY-CELLS

The effects of interleukin-1 beta (IL-1 beta) and tumor necrosis facto r-alpha (TNF alpha) on basal and TRH-induced TSH release; and the effe cts of IL-1 beta on the uptake of [I-125]T-3 and [I-125]T-4 and on nuc lear binding of [I-125]T-3 were examined. Furthermore, the release of other anterior pituitary hormones in the presence of IL-1 beta was mea sured. Anterior pituitary cells from male Wistar rats were cultured fo r 3 days in medium containing 10% FCS. Incubations were performed at 3 7 C in medium with 0.5% BSA for measurement of [I-125]T-3 uptake and w ith 0.1% BSA for measurement of [I-125]T-4 uptake. Exposure to IL-1 be ta (1 pM-1 nM) or TNF alpha (100 pM) for 2-4 h resulted in a significa nt decline in TSH release, which was almost 50% (P < 0.05) for 1 nM IL -1 beta and 24% (P < 0.05) for 100 pM TNF alpha. Measurement of other anterior pituitary hormones (FSH, LH, PRL, and ACTH) in the same incub ation medium showed that IL-1 beta did not alter their release. When t he effects of IL-1 beta (1 pM-1 nM) and TNF alpha (100 pM) on TRH-indu ced TSH release were measured in short term experiments, the inhibitor y effects had disappeared. The addition of 1-100 nM octreotide, a soma tostatin analog, resulted in a decrease in TRH-induced TSH release up to 33% of the control value (P < 0.05). Exposure to dexamethasone (1 n M to 1 mu M) affected basal and TRH-induced TSH release similar to the effect of IL-1 beta. The 15-min uptake of [I-125]T-3 and [I-125]T-4, expressed as femtomoles per pM free hormone, was not affected by the p resence of IL-1 beta (1-100 pM). When IL-1 beta (100 pM) was present d uring 3 days of culture, TSH release was reduced to 88 +/- 2% of the c ontrol value (P < 0.05). This effect was not associated with an altere d [125I]T-3 uptake (15 min to 4 h) or with any change in nuclear T-3 b inding. We conclude that 1) IL-1 beta decreases TSH release by a direc t action on the pituitary; 2) this effect is not due to elevated thyro id hormone uptake or increased T-3 nuclear occupancy; 3) IL-1 beta doe s not affect TRH-induced TSH release or the release of other anterior pituitary hormones; and 4) TNF alpha affects basal and TRH-induced TSH release in the same way as IL-1 beta.