Interactions between thyreostimulin and PAF-acether on thyroid cell metabolism

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1-O-Alkyl, 2-acetyl sn-glycerylphosphorylcholine (platelet activating factor (PAF)-acether) originally described as a platelet activating factor, is effective on various parameters in different cells. It seemed interesting to us to test it on porcine thyroid cells cultured for 1 to 5 days in the absence (control cells) or in the presence of 0.1 mU/ml thyreostimulin (TSH cells). At concentrations ranging from 0.5 to 2.5 μM, PAF-acether inhibited significantly the accumulation of cyclic AMP resulting from a 5 min incubation of the cells with TSH (40 mU/ml) or forskolin (0.1 mM). PAF-acether alone did not affect basal cyclic AMP accumulation. The maximal inhibition was obtained on a 3 day culture and amounted to 40–50%. The inhibition was transient and vanished after a 30 min incubation. The effects of PAF-acether (0.5 μM) on phospholipid metabolism depended closely upon the physiological state of the cells and upon the age of the culture. When PAF-acether was incubated for 2 h with [ 32P]phosphate, it mimicked the effects of TSH, i.e. it increased phosphatidylinositol (PI) labelling on 1 day control cells (expected effect) and decreased it with 1 day TSH cells (reverse effects). The PAF-acether effect was rapid in onset. After cell prelabelling for 2 h in the presence of TSH, PAF-acether added for 15 min completely counteracted the hormone effects on PI and phosphatidylcholine (PC) but increased the phosphatidic acid (PA) labelling. The effect of PAF-acether on PI labelling was partially antagonized by forskolin. Protein iodination, which is very dependent on the culture conditions, reached a very high rate in 3 or 4 day TSH-treated cells. This rate was not markedly enhanced by acute TSH stimulation and was decreased by 37% in 45 min by 2.5 μM PAF. This negative effect was completely abolished in the presence of TSH. On the contrary PAF, like TSH but more efficiently, increased the protein iodination of control cells by 60% in a 45 min period. The positive effect of PAF was not additive to that of TSH. The partial sharing of TSH properties by forskolin on the one hand and PAF on the other suggests that the cyclic AMP-dependent effects of the hormone are controlled by yet uncharacterized agents linked to phospholipid turnover and vice-versa.