Biochemical significance of 19-hydroxytestosterone in the process of aromatization in human corpus luteum.
19-Hydroxyandrogens are known to be an intermediary metabolite in the aromatizing reaction, though the physiological role of this compound has not yet been clarified. In this study, microsomes obtained from human corpus luteum were incubated with testosterone or 19-hydroxytestosterone (19-OHT) as the substrate to investigate the biochemical significance of 19-OHT in the process of aromatization in the ovary. The inhibitory effects of 4-hydroxyandrostenedione (4-OHA) on the formation of estradiol from testosterone and 19-OHT in human ovary were also investigated. When testosterone was incubated with human ovarian microsomes, 19-OHT and estradiol were identified. When 19-OHT was used as the substrate, the formation of estradiol was demonstrated. To our knowledge, this is the first report to demonstrate the formation of estradiol from 19-OHT in human ovarian tissue. The Km value of aromatase for testosterone on human corpus luteum microsomes was 0.21 microM. 4-OHA exhibited inhibition with a Ki of 35 nM. With testosterone and 19-OHT as the substrate, the formation of estradiol was also equally inhibited by 4-OHA. A dose dependent inhibition of estradiol formation was observed, with no apparent accumulation of 19-OHT. These results suggest that 19-OHT may not only be an intermediary metabolite in the aromatization of testosterone by human ovary but could be a product of the microsomal enzyme.
Watanabe
S
S
Department of Obstetrics and Gynecology, Showa University, School of Medicine, Tokyo, Japan.
Tohma
Y
Y
Chiba
H
H
Shimizu
Y
Y
Saito
H
H
Yanaihara
T
T
D000328:Adult; D000735:Androstenedione / Q000031:analogs & derivatives / Q000494:pharmacology; D047072:Aromatase Inhibitors; D003338:Corpus Luteum / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D006915:Hydroxytestosterones / Q000378:metabolism*; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D013739:Testosterone / Q000378:metabolism*
D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors; D006915:Hydroxytestosterones; D013739:Testosterone; D000735:Androstenedione; C036445:19-hydroxytestosterone; D004958:Estradiol; C014594:formestane