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 h as not yet been clarified. In this study, microsomes obtained from hum an corpus luteum were incubated with testosterone or 19-hydroxytestost erone (19-OHT) as the substrate to investigate the biochemical signifi cance of 19-OHT in the process of aromatization in the ovary. The inhi bitory effects of 4-hydroxyandrostenedione (4-OHA) on the formation of estradiol from testosterone and 19-OHT in human ovary were also inves tigated. When testosterone was incubated with human ovarian microsomes , 19-OHT and estradiol were identified. When 19-OHT was used as the su bstrate, the formation of estradiol was demonstrated. To our knowledge , this is the first report to demonstrate the formation of estradiol f rom 19-OHT in human ovarian tissue. The Km value of aromatase for test osterone on human corpus luteum microsomes was 0.21 mu M. 4-OHA exhibi ted 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 1 9-OHT may not only be an intermediary metabolite in the aromatization of testosterone by human ovary but could be a product of the microsoma l enzyme.