Testosterone effects on the induction and urinary excretion of mouse kidney glycosphingolipids associated with lysosomes.

Male C57BL/6J mice were shown to excrete in their urine approximately 50 times as much glycolipid as do female mice. These lipids were primarily galabiglycosylceramides and globotriglycosylceramides which contained nonhydroxy and hydroxy fatty acids, sphingosine, and phytosphingosine as components of their ceramide moieties. The lipids were shown to be associated with multilamellar bodies. Neutral glycosphingolipids from kidney and urine were separated and analyzed by high performance liquid chromatographic techniques. Male kidneys were shown to contain about twice as much neutral glycosphingolipid as female kidneys. The female kidneys were virtually devoid of galactosylceramides and galabiglycosylceramides. Implantation of testosterone pellets in female mice resulted in a concomitant increase in urinary glycosphingolipids (greater than 100-fold) and in urinary lysosomal enzymes (about 10-fold). In mutant light ear mice, which are defective in excretion of lysosomal enzymes, the urinary excretion of glycolipids is also blocked. Taken together these data suggest that testosterone induces the formation of multilamellar kidney lysosomes which contain a complement of glycosphingolipids and which are normally excreted in the urine.