Involvement of prostaglandins in the inhibition of growth hormone production in cultured pituitary cells by insulin.

The effect of insulin was tested on the rate of synthesis and release of growth hormone in cultured rat anterior pituitary cells. Concentrations of insulin between 10(-9) and 10(-7) mol/l (6--600 ng/ml or 0.15--15 mu./ml) inhibited synthesis of growth hormone; 10(-8) mol insulin/l was most effective. The effect was observed after a time-lag of at least 1 h. Insulin at concentrations between 3 x 10(-9) mol/l and 3 x 10(-7) mol/l also inhibited growth hormone secretion in 30 min incubations. The most effective insulin concentration in this case was 3 x 10(-8) mol/l. Insulin (10(-9)-10(-7) mol/l) also decreased the intracellular content of prostaglandins E and F. The effect was rapid, reaching a maximum after 30 min. Indomethacin, an inhibitor of prostaglandin synthetase, dramatically lowered the concentration of prostaglandins in the cells within 30 min; growth hormone synthesis was also decreased, but not until after 2 h of incubation. The results suggest that an initial response to insulin treatment is a lowering of intracellular levels of prostaglandins, which may then mediate a decrease in growth hormone synthesis, after a 1--2 h delay.