[Inhibition of testosterone metabolism by 17-alpha-estradiol in rat liver slices].
Inhibition of the Testosterone Metabolism in Rat Liver Slices by 17 alpha-Estradiol. The influence of 17 alpha-estradiol (CAS 57-91-0), a hormonally almost inactive isomer of physiological 17 beta-estradiol, on the metabolism of [14C]-labeled testosterone in rat liver slices was investigated. The analysis of extracts from incubates (3.0 ml medium, 100 mg liver slices, 416 nmol [14C]-testosterone, 0.1-30 micrograms 17 alpha-estradiol, 37 degrees C, 30 min) by thin layer chromatography showed, that 30 micrograms of 17 alpha-estradiol inhibited the testosterone turnover in liver slices of female animals. The failure of a significant inhibitory effect in liver slices of male animals is attributed to the known, much smaller total turnover of testosterone in male liver cells. The amount of unchanged 4-en-3-oxo-steroid (testosterone and 4-androstene-3,17-dione) was increased by a factor of 2.65 and 2.25, respectively. With high probability, the inhibition was the result of a decreased hydrogenation of testosterone to dihydrotestosterone (DHT, 17 beta-hydroxy-5 alpha-androstan-3-one), catalyzed by 5 alpha-reductase, since the production rates of DHT and the DHT-transformation metabolites (5 alpha-androstane-3 alpha,17 beta-diol and 5 alpha-androstane-3,17-dione) were significantly lowered (factors: 0.16, 0.61, 0.61, respectively). In further experiments 17 beta-estradiol and 17 alpha-ethinylestradiol could be shown to inhibit the testosterone turnover in liver slices of female rats, too, but to a lower extent that 17 alpha-estradiol (relative inhibitory effects: 17 alpha-estradiol:17 beta-estradiol:17 alpha-ethinylestradiol = 100 : 73 : 58).(ABSTRACT TRUNCATED AT 250 WORDS)
Schriefers
H
H
Institut für Physiologische Chemie, Universitätsklinikum Essen.
Wright
M C
MC
Rozman
T
T
Hevert
F
F
D000818:Animals; D002855:Chromatography, Thin Layer; D004958:Estradiol / Q000494:pharmacology*; D004997:Ethinyl Estradiol / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013739:Testosterone / Q000378:metabolism*
D013739:Testosterone; D004997:Ethinyl Estradiol; D004958:Estradiol
Hemmung des Testosteron-Stoffwechsels durch 17 alpha-Estradiol in Rattenleberschnitten.