Immature ovaries and polycystic kidneys in the congenital polycystic kidney mouse may be due to abnormal sex steroid metabolism

Ke 6 is a 17 beta -hydroxysteroid dehydrogenase (17 beta HSD) that is expre ssed in the kidneys and gonads. The expression of this gene is markedly red uced in three murine models of recessive polycystic kidney disease, a devel opmental disorder, where some nephrons within the affected kidneys develop into huge fluid-filled cysts while the non-cystic nephrons atrophies by apo ptosis. Here, we show that in the cpk/cpk mouse, which have polycystic kidn eys, the female reproductive organs also fail to mature properly and remain arrested at an early stage of development. Direct measurement of 17 beta H SD activity showed a severe reduction in estrogen and androgen metabolism w ithin gonadal and non-gonadal tissues of the cpk/cpk mouse. Using immunoflu orescent staining we localized the expression of the Ke 6 protein within th e female mouse reproductive organs. Our findings suggest that estrogen/andr ogen metabolism may play an important role in the development of the urogen ital systems. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.