Effects of the aromatase inhibiting delta 1,4-bisnorcholadienic acid on the steroid biosynthesis in the human ovary in vitro.
Ключови думи
Резюме
Compounds capable of limiting oestrogen production may be useful for controlling fertility and growth of oestrogen-dependent tumors. To examine the direct effects of the aromatase inhibiting delta 1,4-bisnorcholadienic acid on the ovarian biosynthesis of steroids, tissue slices obtained from two cyclically functional human ovaries were incubated with [4-14C]pregnenolone as precursor. The steroid production was determined by measuring the concentration of eleven 14C-labelled steroids in the medium at the end of a 3-h incubation. In the ovary from the follicular phase the addition of delta 1,4-bisnorcholadienic acid to the incubation medium inhibited the biosynthesis of androstenedione, whereas the biosynthesis of 17 alpha-hydroxypregnenolone, dehydroepiandrosterone and androstenediol slightly increased. In the luteal ovary the in vitro-synthesis of progesterone, 17 alpha-hydroxyprogesterone, oestrone and oestradiol-17 beta was inhibited by delta 1,4-bisnorcholadienic acid. The principal manifestation of the effects of delta 1,4-bisnorcholadienic acid on the biosynthesis of steroids is an apparent inhibition of the 3 beta-hydroxysteroid dehydrogenase-delta 5-4-isomerase (3 beta-HSD) activity. The reduced production of oestrogens can be caused by an inhibition of the aromatase and/or the inhibition of the 3 beta-HSD activity. It is noteworthy, that the effects of the delta 1,4-bisnorcholadienic acid on the steroidogenesis in the human ovary are similar to those effects previously published for progestagens and the "pure antiandrogen" cyproterone. The results indicate, that the delta 1,4-bisnorcholadienic acid act directly on the steroid biosynthesis in the human ovary in vitro.