Inhibitory effects of delta 9-tetrahydrocannabinol on glycolytic substrates in the rat testis

Experiments conducted with a rat testicular tissue indicated that delta 9-tetrahydrocannabinol (THC) produced a dose-dependent inhibition of glucose metabolism. Incubation of testicular tissue with different U-14C-fructose concentrations and 0.3 mM THC also significantly inhibited 14CO2 production; however, testicular utilization of 214C-pyruvate remained unaffected by THC. In other experiments, 0.3 mM THC significantly decreased tissue concentrations of dihydroxyacetone phosphate, fructose-1,6-diphosphate, and glucose-6-phosphate by 23, 31 and 29%, respectively. Uptake studies with 14C-2-deoxy-D-glucose showed a 43% reduction in uptake of this substrate by testicular tissue in the presence of 0.3 mM THC. These studies demonstrate that THC has an inhibitory effect on the utilization of energy substrates by the testis. Sites of THC action may be the membrane uptake step, the hexokinase step, and/or possible the phosphofructokinase step. It is proposed that this inhibition of testicular glycolysis could deprive the cells of their energy reserves and thereby may disrupt many gonadal functions.