CHARACTERIZATION OF KE-6, A NEW 17-BETA-HYDROXYSTEROID-DEHYDROGENASE,AND ITS EXPRESSION IN GONADAL TISSUES

The abnormal regulation of the Ke 6 gene has been linked to the develo pment of recessive polycystic kidney disease in the mouse. In this rep ort, we have shown that Ke 6 is a 17 beta-hydroxysteroid dehydrogenase and can regulate the concentration of biologically active estrogens a nd androgens. The Ke 6 enzyme is preferentially an oxidative enzyme an d inactivates estradiol, testosterone, and dihydrotestosterone. Howeve r, the enzyme has some reductive activity and can synthesize estradiol from estrone. We find that the Ke 6 gene is expressed within the ovar ies and testes. The presence of Ke 6 protein within the cumulus cells surrounding the oocyte places it in a strategic location to control th e level of steroids to which the egg is exposed. Previously, it had be en shown that glucocorticoids can induce renal cysts in the neonatal r odent, only when given at a narrow time window of postnatal kidney dev elopment. We propose that the reduction in the level of Ke 6 enzyme, w hich occurs in the cpk, jck, and pcy mice, may lead to abnormal elevat ions in local level of sex steroids, which either directly or indirect ly via abnormal glucocorticoid metabolism result in recessive renal cy stic disease, a developmental disorder of the kidney.