CHARACTERIZATION OF THE PRODUCTS OF A GENE EXPRESSED DURING ANDROGEN-PROGRAMMED CELL-DEATH AND THEIR POTENTIAL USE AS A MARKER OF UROGENITAL INJURY

Regression of the rat ventral prostate gland following castration is accompanied by the induced expression of messenger RNA encoding Testosterone Repressed Prostate Message-2 (TRPM-2). Subsequent studies have shown that this gene is also induced during renal injury. In each of these tissues, the TRPM-2 RNA products are expressed by cells undergoing programmed death as a result of the hormonal stimuli or the traumatic insult. In an attempt to characterize this gene and its products, we partially sequenced complementary DNAs for TRPM-2 isolated from a recombinant library constructed using RNA of a hydronephrotic kidney. The sequence of these clones showed close homology with the sulfated glycoprotein-2 (SGP-2/clusterin) gene, expressed constitutively by mammalian Sertoli cells. Antibody recognition studies confirm this homology. Antiserum made against rat clusterin recognized TRPM-2 encoded polypeptides in extracts of regressing rat ventral prostate glands. Western blot analysis allowed us to demonstrate large increases in the concentration of these proteins in extracts of regressing ventral prostate gland and in rat serum and urine during the acute period of prostatic regression. These results indicate that proteins are synthesized from the large amount of TRPM-2 RNA produced by dying prostate cells and imply that these proteins are shed into the serum and urine. Based on the intense synthesis of TRPM-2 gene products by dying cells in the urogenital tract and the ability to assay for these products in serum and urine, we suggest that an assay for TRPM-2 products might allow us to monitor the extent of cellular damage associated with specific urogenital disease states.