Effects of the Aromatase Inhibiting Δ^1,4 -Bisnorcholadienic Acid on the Steroid Biosynthesis in the Human Ovary in Vitro

Summary

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 Δ^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 Δ^1,4-bisnorcholadienic acid to the incubation medium inhibited the biosynthesis of androstenedione, whereas the biosynthesis of 17α-hydroxy-pregnenolone, dehydroepiandrosterone and androstenediol slightly increased. In the luteal ovary the in vitro-synthesis of progesterone, 17α-hydroxyprogesterone, oestrone and oestradiol-17β was inhibited by Δ^1,4-bisnorcholadienic acid.

The principal manifestation of the effects of Δ^1,4-bisnorcholadienic acid on the biosynthesis of steroids is an apparent inhibition of the 3β-hydroxysteroid dehydrogenase-Δ^5-4-isomerase (3β-HSD) activity. The reduced production of oestrogens can be caused by an inhibition of the aromatase and/or the inhibition of the 3β-HSD activity. It is noteworthy, that the effects of the Δ^1,4-bisnor-choladienic 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 Δ^1,4-bisnorcholadienic acid act directly on the steroid biosynthesis in the human ovary in vitro.

Key words

Steroid biosynthesis - human ovary - aromatase inhibitor