Expression of cytochrome P450c17 and other steroid-converting enzymes in the rat kidney throughout the life-span.
We have investigated the metabolism of [14C]-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: 5alpha-reductase, cytochromes P450c17 and P450c21, 3beta-hydroxysteroid dehydrogenase (HSD)/delta5-delta4 isomerase, and 17beta- and 20alpha-HSDs, catalyzing reductive reactions. The major P4 metabolites were 5alpha-reduced C21 steroids, whose formation was almost completely suppressed by the 5alpha-reductase 4-azasteroid inhibitor, PNU 156765. Androstenedione and testosterone were also formed via 17alpha-hydroxyprogesterone, together with 11-deoxycorticosterone and 20alpha-dihydroprogesterone. DHEA was mainly converted to androst-5-ene-3beta,17beta-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.
Dalla Valle
Luisa
L
Comparative Endocrinology Laboratory, Department of Biology, University of Padova, Via U. Bassi 58/B, 35131, Italy. luisadv@mail.bio.unipd.it
Toffolo
Vania
V
Vianello
Silvia
S
Belvedere
Paola
P
Colombo
Lorenzo
L
D015096:3-Hydroxysteroid Dehydrogenases / Q000096:biosynthesis; D000375:Aging; D000728:Androgens / Q000378:metabolism; D000736:Androstenes / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001378:Azasteroids / Q000494:pharmacology; D015152:Blotting, Northern; D015153:Blotting, Western; D042944:Cholestenone 5 alpha-Reductase / Q000378:metabolism; D002845:Chromatography; D003687:Dehydroepiandrosterone / Q000494:pharmacology; D005260:Female; D007668:Kidney / Q000201:enzymology*; D008297:Male; D009097:Multienzyme Complexes / Q000096:biosynthesis; D011375:Progesterone Reductase / Q000096:biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013254:Steroid 17-alpha-Hydroxylase / Q000096:biosynthesis*; D013255:Steroid 21-Hydroxylase / Q000096:biosynthesis; D013251:Steroid Isomerases / Q000096:biosynthesis; D013256:Steroids / Q000378:metabolism*; D013997:Time Factors; D014018:Tissue Distribution
C088574:(22RS-N-1,1,1-trifluoro-2-phenylprop-2-yl)-3-oxo-4-aza-5alpha-androst-1-ene-17beta-carboxamide; C021425:3 beta-hydroxysteroid oxidoreductase-delta(5) 3-ketosteroid isomerase; D000728:Androgens; D000736:Androstenes; D001378:Azasteroids; D009097:Multienzyme Complexes; D012333:RNA, Messenger; D013256:Steroids; D003687:Dehydroepiandrosterone; D015096:3-Hydroxysteroid Dehydrogenases; D011375:Progesterone Reductase; D013255:Steroid 21-Hydroxylase; D013254:Steroid 17-alpha-Hydroxylase; D042944:Cholestenone 5 alpha-Reductase; D013251:Steroid Isomerases