Expression of cytochrome P450c17 and other steroid-converting enzymes in the rat kidney throughout the life-span

Abstract

We have investigated the metabolism of [ 14 C ]-labelled progesterone (P4) and dehydroepiandrosterone (DHEA) by kidney tissues of newborn and 7-, 15-, 30-, 60- and 365-day-old rats of both sexes. The following enzymes were revealed at all ages by radiochemical identification of the corresponding products: 5α-reductase, cytochromes P450c17 and P450c21, 3β-hydroxysteroid dehydrogenase (HSD)/Δ 5–Δ 4 isomerase, and 17β- and 20α-HSDs, catalyzing reductive reactions. The major P4 metabolites were 5α-reduced C 21 steroids, whose formation was almost completely suppressed by the 5α-reductase 4-azasteroid inhibitor, PNU 156765. Androstenedione and testosterone were also formed via 17α-hydroxyprogesterone, together with 11-deoxycorticosterone and 20α-dihydroprogesterone. DHEA was mainly converted to androst-5-ene-3β,17β-diol, with smaller amounts of the above androgens. Cytochrome P450c17 mRNA and protein were demonstrated by Northern blotting and Western blotting analyses, respectively. P450c17 mRNA, assessed by Northern blotting, protein and catalytic activity all peaked in the kidney samples at 15 days of life and declined thereafter. Cytochrome P450arom was below the level of detection of semi-quantitative RT-PCR. Since the rat kidney has been previously shown to contain cytochrome P450scc as well as androgen and estrogen receptors, it is suggested that it is capable of autonomous hormonal steroidogenesis and that renal steroids, or nephrosteroids, may act locally, in a paracrine or autocrine fashion.