Inhibition of polyamine synthesis blocks urinary secretion of β-glucuronidase from mouse kidney

Abstract

The effect of inhibition of polyamine synthesis on castrated male mouse kidney β-glucuronidase induction and secretion by testosterone was studied. Inhibition of the activities of polyamine synthesis key-enzymes, L-ornithine and S-adenosyl-L-methionine decarboxylases, was performed with the combined treatment of 2-difluoromethylornithine and methylglyoxal bis (guanylhydrazone). Blockage of polyamine synthesis did not affect testosterone-induced increase in renal β-glucuronidase but blocked its secretion into the urine. After withdrawal of inhibitor-treatment β-glucuronidase secretion normalized, and repeated testosterone administration produced undisturbed β-glucuronidase secretion peak in urine suggesting that blockage of β-glucuronidase secretion was not due to the tissue damage produced by inhibitors. These results indicate that the stimulation of renal polyamine synthesis by testosterone is not necessary for the induction of β-glucuronidase but is required for the urinary secretion of this protein.