Peptidases in the kidney and urine of rats after castration

The localization of various peptidases in the renal section of the rat was investigated histochemically, and their activities were determined fluorometrically in renal homogenate. The membrane-bound peptidases aminopeptidase A (APA), aminopeptidase M (APM), gamma-glutamyl-transferase (gamma-GT), dipeptidylpeptidase IV (DAP IV), and the lysosomal dipeptidyl peptidases I (DAP I) and II (DAP II) were investigated in male and female (estrus) rats both before and 30 days after castration. In addition, protein excretion and APA, APM, DAP I and DAP IV activities were measured in the urine of these animals. Histochemically, the membrane-bound peptidases are demonstrable mainly in the brush borders of the proximal tubules. In addition, APA and DAP IV are found in the glomeruli, gamma-GT and DAP IV in the thin descending limbs of the loops of Henle, and gamma-GT in the basal labyrinth of the S2 and S3 segments. The lysosomal peptidases are most concentrated in the S1 and S2 segments of the proximal tubule, in the distal tubule, and in certain cells of the connecting tubule and collecting duct, where they are contained in lysosomes of varying size. Sex differences and castration effects are demonstrable both histochemically and biochemically for the investigated peptidases. Histochemically these effects are most pronounced in the S3 segments for the membrane-bound peptidases, and in the lysosomes of the proximal tubule for the lysosomal peptidases. Biochemical tests in controls show significantly higher lysosomal peptidase activities in the renal homogenate of females than of males. After castration the lysosomal peptidase activities in males increase, approaching those of females. This appears to have bearing on the sex-dependent proteinuria in rats, for lysosomal peptidases and proteinases are particularly important in the degradation of filtered proteins that are reabsorbed in the proximal tubule. In females high lysosomal peptidase activities correlate with a low proteinuria, while males demonstrate lower lysosomal peptidase activities and a significantly higher proteinuria than females. After castration, the lysosomal peptidase activities and proteinuria in males approach those in females. Renal peptidases are also excreted in the urine, again with sex differences, and so these excreted peptidases contribute to the proteinuria in rats.