Effects of cyproterone on the steroid biosynthesis in the human ovary in vitro.

Abstract

To examine the direct effects of cyproterone 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. Under control conditions, the in vitro-synthesis of 17 alpha-hydroxypregnenolone, dehydroepiandrosterone, androstenediol (5-ene-3 beta-hydroxy-steroids) and androstenedione represents the characteristic profile of steroids of the ovary from the follicular phase. The addition of cyproterone to the incubation medium inhibited the biosynthesis of androstenedione, whereas 17 alpha-hydroxypregnenolone and dehydroepiandrosterone increased. The in vitro-synthesis of progesterone, 17 alpha-hydroxyprogesterone, oestrone and oestradiol-17 beta represents the characteristic profile of steroids of the luteal ovary. The biosynthesis of progesterone, 17 alpha-hydroxyprogesterone and oestradiol-17 beta is inhibited by cyproterone. The principal manifestation of the effects of cyproterone on the two different profiles of steroids is an apparent inhibition of the 3 beta-hydroxysteroiddehydrogenase-delta 5-4-isomerase activity. It is noteworthy, that the effects of the "pure antiandrogen" cyproterone are similar to those effects previously published for progestagens (chlormadinone acetate, norethisterone acetate and D-norgestrel). A simplified concept of the direct effects of cyproterone and progestagens on the steroidogenesis in the human ovary is proposed. The results indicate, that cyproterone, in addition to its well-known androgen receptor blocking effect, act directly on the steroid biosynthesis in the human ovary in vitro.