In vitro metabolism of testosterone by cultured Sertoli cells and the effect of FSH.
Cultures of Sertoli cells isolated from testes of 18-and 36-day-old Long Evans rats were used to investigate their capacity to metabolize testosterone and the effect of FSH on such metabolism. Three different approaches were used: 1) investigation of the metabolism of radiolabeled testosterone under saturating substrate conditions; 2) study of the metabolism of radiolabeled testosterone utilizing trace amounts of high specific activity substrates; 3) the utilization of radioimmunoassay for measurement of estradiol-17 beta. The following steroids were isolated and identified by recrystallization to constant specific acitvity from the control and FSH-treated cultures; testosterone (unconverted substrate), androstenedione, dihydrotestosterone, 3 alpha-hydroxy-5 alpha-androstan-17-one and 5 alpha-androstane-3 alpha, 17 beta-diol. Radioimmunoassay data suggests that the Sertoli cells produce an estradiol-17 beta-like compound from unlabeled testosterone and that this production is stimulated by FSH. However, the radioactive metabolite from all our studies that behaved chromatographically like estradiol--17 beta failed to crystallize to constant specific activity, while in each experiment, authentic radiolabeled estradiol-17 beta added as recovery tracer did. The data demonstrate that : 1) cultures of Sertoli cells from immature rats have 5 alpha-reductase, 3 alpha- and 17 beta-hydroxysteroid oxidoreductase activities; 2) these enzymes may be affected by FSH; 3) based on radiolabeled metabolic techniques, Sertoli cells were unable to biotransform testosterone to estradiol-17 beta even in the presence of FSH.
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism; D000728:Androgens / Q000096:biosynthesis; D000818:Animals; D002478:Cells, Cultured; D004958:Estradiol / Q000096:biosynthesis; D005640:Follicle Stimulating Hormone / Q000494:pharmacology*; D008297:Male; D011863:Radioimmunoassay; D051381:Rats; D012708:Sertoli Cells / Q000187:drug effects / Q000378:metabolism*; D013254:Steroid 17-alpha-Hydroxylase / Q000378:metabolism; D013250:Steroid Hydroxylases / Q000378:metabolism; D013739:Testosterone / Q000378:metabolism*
D000728:Androgens; D013739:Testosterone; D004958:Estradiol; D005640:Follicle Stimulating Hormone; D013250:Steroid Hydroxylases; D013254:Steroid 17-alpha-Hydroxylase; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase