EFFECTS OF INHIBIN ON ACTIVIN A-INDUCED GLUCOSE-METABOLISM IN RAT HEPATOCYTES

This study was conducted to investigate the effects of inhibin on hepa tic glucose metabolism. We have previously reported that activin A ind uced a dose-dependent glycogenolytic action on hepatocytes, and that 1 0(-9)M activin A induced a maximum glycogenolytic effect. Inhibin itse lf induced no increase or decrease in glucose output at any dose teste d. At a concentration of 10(-10)M, inhibin was seen to inhibit 10(-9)M activin A-induced glucose output by 30% as compared to the control. I n contrast to its inhibitory effect on the action of activin A, 10(-10 )M and higher concentrations of inhibin did not inhibit angiotensin II - or vasopressin-induced glycogenolysis. We further investigated the m echanism of the inhibitory effect of inhibin on activin A-induced glyc ogenolysis, and found that 10(-10)M inhibin did inhibit the increase i n cytoplasmic-free calcium concentration that was seen with 10(-9)M ac tivin A. We also investigated the effects of inhibin on the activin A- induced production of inositol trisphosphates, and the results showed that 10(-10)M inhibin inhibited the activin A-induced production of in ositol trisphosphates by 30% compared to the control. Furthermore, it was demonstrated that inhibin did not affect the binding of activin A to isolated hepatocytes. These data demonstrated that inhibin inhibite d the activin A-induced glycogenolysis by inhibiting the increases of inositol trisphosphates and cytoplasmic free calcium concentrations.