ANDROGEN METABOLISM IN CULTURED RAT RENAL INNER MEDULLARY COLLECTING DUCT (IMCD) CELLS

Although the stimulations of renal hypertrophy and renal erythropoieti n production have been well-known androgen effects in the kidney, rece nt investigative progresses are further providing good evidences for a ndrogen-regulated gene productions of key enzymes or local hormone sub strates important to renal cell metabolisms and tubular functions in m ouse or rat proximal tubules, respectively. It has been also reported that testosterone restores vasopressin receptors in medullary collecti ng ducts of the ageing I nt and improves a urinary concentrating abili ty. Therefore in the present study we examined a metabolic pathway of androgens in cultured rat renal IMCD cells, which finally determine a urinary composition and volume. IMCD cells cultured from kidneys of ma le Wistar rats weighing about 200 g were incubated with serum-free cul ture media containing 4 nM [H-3] testosterone or [H-3] androstenedione for 2-48 h. Radioactive compounds in incubation media were then separ ated by reverse-phase high-pressure liquid chromatography (HPLC) and i dentified mainly on the basis of comparison of retention times of stan dard materials on HPLC. The main metabolites identified in testosteron e or androstenedione incubation experiment were 5 alpha-dihydrotestost erone or 5 alpha-androstanedione, respectively. 5 alpha-Reductase inhi bitor; MK 906, effectively inhibited the formations of these Ring A re duced metabolites. These results may suggest that rat renal IMCD cells possess 5 alpha-reductase activity, thereby converting androgens into their biologically active forms in vivo. (C) 1998 by Elsevier Science Inc.