Effects of interleukin-1β on thyrotropin secretion and thyroid hormone uptake in cultured rat anterior pituitary cells

The effects of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNFα) on basal and TRH-induced TSH release, and the effects of IL-1β on the uptake of [ 125I]T 3 and [ 125I]T 4 and on nuclear binding of [ 125I]T 3 were examined. Furthermore, the release of other anterior pituitary hormones in the presence of IL-1β was measured. Anterior pituitary cells from male Wistar rats were cultured for 3 days in medium containing 10% FCS. Incubations were performed at 37 C in medium with 0.5% BSA for measurement of [ 125I]T 3 uptake and with 0.1% BSA for measurement of [ 125I]T 4 uptake. Exposure to IL-1β (1 pM-1 nM) or TNFα (100 pM) for 2- 4 h resulted in a significant decline in TSH release, which was almost 50% (P < 0.05) for 1 nM IL-1β and 24% (P < 0.05) for 100 pM TNFα. Measurement of other anterior pituitary hormones (FSH, LH, PRL, and ACTH) in the same incubation medium showed that IL-1β did not alter their release. When the effects of IL-1β (1 pM-1 nM) and TNFα (100 pM) on TRH-induced TSH release were measured in short term experiments, the inhibitory effects had disappeared. The addition of 1-100 nM octreotide, a somatostatin analog, resulted in a decrease in TRH-induced TSH release up to 33% of the control value (P < 0.05). Exposure to dexamethasone (1 nM to 1 μM) affected basal and TRH-induced TSH release similar to the effect of IL-1β. The 15-min uptake of [ 125I]T 3 and [ 125I]T 4, expressed as femtomoles per pM free hormone, was not affected by the presence of IL-1β (1-100 pM). When IL-1β (100 pM) was present during 3 days of culture, TSH release was reduced to 88 ± 2% of the control value (P < 0.05). This effect was not associated with an altered [ 125I]T 3 uptake (15 min to 4 h) or with any change in nuclear T 3 binding. We conclude that 1) IL-1β decreases TSH release by a direct action on the pituitary; 2) this effect is not due to elevated thyroid hormone uptake or increased T 3 nuclear occupancy; 3) IL-1β does not affect TRH- induced TSH release or the release of other anterior pituitary hormones; and 4) TNFα affects basal and TRH-induced TSH release in the same way as IL- 1β.

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