Effects of the aromatase inhibiting delta 1,4-bisnorcholadienic acid on the steroid biosynthesis in the human ovary in vitro.

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.