| Abstract: | TRH stimulated the metabolism of lipids of the phosphatidylinositol (PI)-phosphatidic acid (PA) cycle and caused an increase in the level of free or unesterified arachidonic acid in mouse pituitary thyrotropic tumor (TtT) cells. In cells labeled with 32P]orthophosphate for 45 min, TRH caused a rapid specific increase in 32P]PA to 190 +/- 8% (+/- SE) of the control value at 15 sec (P less than 0.005) and in 32P]PI to 158 +/- 8% at 2 min (P less than 0.005). In cells labeled to isotopic steady state with 3H]inositol, TRH caused a decrease in 3H]PI to 92 +/- 1.8% of the control value at 1 min (P less than 0.01) and increased the level of 3H]inositolmonophosphate. In cells labeled to isotopic steady state with 14C]stearic acid, TRH caused a transient rise in 14C]diacylglycerol and a more prolonged increase in 14C]PA. In cells labeled to isotopic steady state with 3H]arachidonic acid, TRH stimulated a rise in free 3H]arachidonic acid to 210 +/- 8% of the control value at 15 sec (P less than 0.001), with a return to a level of 125 +/- 2% of the control value by 5 min. Arachidonic acid added exogenously caused efflux of 45Ca2+ from prelabeled cells and stimulated TSH secretion. Hence, in TtT cells, TRH 1) rapidly stimulated a decrease in the level of PI and increased inositolmonophosphate, diacylglycerol, and PA; and 2) caused a rapid increase in the level of free arachidonic acid. These effects may be important in stimulation of TSH secretion by TRH. Because arachidonic acid, when added exogenously, mobilized cellular Ca2+ and stimulated TSH secretion, arachidonic acid may mediate, at least in part, TRH-stimulated TSH secretion. The action of TRH on lipid metabolism in TtT cells is different from that in mammotropic pituitary cells, since TRH does not cause an increase in the level of free arachidonic acid in GH3 cells. |
