Androgen metabolism in cultured rat renal inner medullary collecting duct (IMCD) cells.
Although the stimulations of renal hypertrophy and renal erythropoietin production have been well-known androgen effects in the kidney, recent investigative progresses are further providing good evidences for androgen-regulated gene productions of key enzymes or local hormone substrates important to renal cell metabolisms and tubular functions in mouse or rat proximal tubules, respectively. It has been also reported that testosterone restores vasopressin receptors in medullary collecting ducts of the ageing rat and improves a urinary concentrating ability. 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 male Wistar rats weighing about 200 g were incubated with serum-free culture media containing 4 nM [3H] testosterone or [3H] androstenedione for 2-48 h. Radioactive compounds in incubation media were then separated by reverse-phase high-pressure liquid chromatography (HPLC) and identified mainly on the basis of comparison of retention times of standard materials on HPLC. The main metabolites identified in testosterone or androstenedione incubation experiment were 5 alpha-dihydrotestosterone or 5 alpha-androstanedione, respectively. 5 alpha-Reductase inhibitor, MK 906, effectively inhibited the formations of these Ring A reduced 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.
Matsuzaki
K
K
Third Department of Internal Medicine, Teikyo University School of Medicine, Chiba, Japan.
Arai
T
T
Inumaru
T
T
Mihori
M
M
Momose
T
T
Sano
M
M
Koide
K
K
Shimizu
N
N
D058891:5-alpha Reductase Inhibitors; D000728:Androgens / Q000378:metabolism*; D000735:Androstenedione / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D016895:Culture Media, Serum-Free; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018120:Finasteride / Q000494:pharmacology; D007679:Kidney Medulla / Q000378:metabolism*; D007685:Kidney Tubules, Collecting / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013739:Testosterone / Q000378:metabolism; D014316:Tritium
D058891:5-alpha Reductase Inhibitors; D000728:Androgens; D016895:Culture Media, Serum-Free; D004791:Enzyme Inhibitors; D014316:Tritium; D013739:Testosterone; D000735:Androstenedione; D018120:Finasteride