Arakawa S, Mitsuma M, Iyo M, Ohkawa R, Kambegawa A, Okinaga S, Arai K
Department of Obstetrics and Gynecology, Teikyo University School of Medicine, Tokyo, Japan.
Endocrinol Jpn. 1989 Jun;36(3):387-94. doi: 10.1507/endocrj1954.36.387.
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 3 beta-hydroxy steroid dehydrogenase (3 beta-HSD), or with PMS for 17 alpha-hydroxylase and 17,20 lyase. The substrates used were pregnenolone (P5) for 3 beta-HSD, progesterone (P4) for 17 alpha-hydroxylase, and 17 alpha-hydroxy-progesterone (17 alpha-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 3 beta-HSD, and the inhibition by gestrinone (Ki = 3.0 microM) and 3-keto-desogestrel (17.5 microM) was particularly marked. Only desogestrel (Ki = 30.3 microM) and danazol (168 microM) inhibited 17 alpha-hydroxylase. All the steroids inhibited 17,20 lyase, and the inhibition by desogestrel (Ki = 0.70 microM), danazol (0.80 microM), and gestrinone (30 microM) was particularly marked.
合成孕激素或达那唑治疗子宫内膜异位症的作用部位主要被认为是下丘脑 - 垂体水平，但也有人提出它们对子宫内膜和卵巢有直接作用。我们研究了这些合成类固醇对大鼠卵巢类固醇生成酶的影响。在体外研究了炔诺酮、左炔诺孕酮、达那唑、孕三烯酮、去氧孕烯和3 - 酮去氧孕烯的作用。酶的来源是从未成熟大鼠的卵巢制备的，这些大鼠用孕马血清促性腺激素（PMS）和人绒毛膜促性腺激素（hCG）处理以获得3β - 羟基类固醇脱氢酶（3β - HSD），或只用PMS处理以获得17α - 羟化酶和17,20 - 裂解酶。用于3β - HSD的底物是孕烯醇酮（P5），用于17α - 羟化酶的底物是孕酮（P4）以及用于17,20 - 裂解酶的底物是17α - 羟基孕酮（17α - OH - P4）。将底物与酶来源和辅酶一起孵育，并测量形成的产物。所有类固醇均抑制了
