Inhibition of Rat Ovarian 3β-Hydroxysteroid Dehydrogenase (3β-HSD), 17α-Hydroxylase and 17, 20 Lyase by Progestins and Danazol

Abstract

The site of action of synthetic progestins or danazol in the treatment of endometriosis is considered to be mainly the hypothalamo-pituitary level, but the direct action to the uterine endometrium and the ovary is also suggested. We investigated the effect of these synthetic steroids to rat ovarian steroidogenic enzymes. The effect of norethisterone, levonorgestrel, danazol, gestrinone, desogestrel and 3-keto-desogestrel was studied in vitro. The sources of the enzymes were prepared from ovaries of immature rats treated either with pregnant mare serum gonadotropin (PMS) and human chorionic gonadotropin (hCG) for 3β-hydroxy steroid dehydrogenase (3β-HSD), or with PMS for 17α- hydroxylase and 17,20 lyase. The substrates used were pregnenolone (P5) for 3β-HSD, progesterone (P4) for 17α-hydroxylase, and 17α-hydroxy-progesterone (17α-OH-P4) for 17,20 lyase. The substrates were incubated with the enzyme sources and coenzymes, and the products formed were measured. All the steroids inhibited 3β-HSD, and the inhibition by gestrinone (Ki= 3.0 μM) and 3-keto-desogestrel (17.5 μM) was particularly marked. Only desogestrel (Ki= 30.3 μM) and danazol (168 μM) inhibited 17α-hydroxylase. All the steroids inhibited 17,20 lyase, and the inhibition by desogestrel (Ki= 0.70 μM), danazol (0.80 μM), and gestrinone (30μM) was particularly marked. © 1989, The Japan Endocrine Society. All rights reserved.