Danazol Inhibits Steroidogenesis in the Rat Testisin Vitro
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Danazol suppressed LH-stimulated testosterone and androstenedione production in rat Leydig cells and directly inhibited multiple microsomal enzymes involved in testicular steroidogenesis <i>in vitro</i>.
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Abstract
The effects of danazol on steroidogenesis in vitro in the rat testis were examined by studying: 1) androgen synthesis in rat Leydig cells cultured with danazol, 2) danazol binding to rat testis microsomal cytochrome P-450, and 3) enzyme kinetics of danazol inhibition of the microsomal enzymes of testicular steroidogenesis. Concentrations of danazol as low as 1 micrometer suppressed LH-stimulated testosterone and androstenedione production in cultured Leydig cells. The addition of danazol to a preparation of testicular microsomes elicited a type I cytochrome P-450 binding spectrum, with an apparent spectral dissociation constant (Ks) of 4.8 micrometer. Danazol inhibited progesterone and 17alpha-hydroxy-progesterone binding to microsomal P-450 with apparent spectral inhibition constants of 2.4 micrometer and 2.8 micrometer, respectively. Danazol competitively inhibited 3beta-hydroxy-delta5-steroid dehydrogenase-isomerase (apparent enzymatic inhibition constant, KI = 5.8 micrometer), 17alpha-hydroxylase (KI = 2.4 micrometer), 17,20 lyase (KI = 1.9 micrometer), and 17beta-hydroxysteroid dehydrogenase (KI = 4.4 micrometer). These findings indicate that low concentrations of danazol directly inhibit steroidogenesis in the rat testis in vitro.
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References (8)
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Cited by (26)
- Danazol 2022
- Short-term dynamic culture of rat testicular fragments as a model to assess effects on steroidogenesis—Potential use and limitations 2009
- A Benefit-Risk Assessment of Medical Treatment for Uterine Leiomyomas 2002
- Effects of danazol on DNA synthesis in rat prostate 1993
- Effects of Danazol on endometrial DNA synthesis in rats 1993
- Suppression of the development of uterine adenomyosis by danazol treatment in mice 1992
- The use of danazol as a treatment of endometriosis 1991
- Effects of an androgenic derivative on pre-established mammary tumours chemically induced in the rat 1991
- Comparison of the pharmacology of nafarelin and danazol 1990
- Effects of danazol on steroidogenesis and gonadotropic responsiveness in isolated human preovulatory follicular cells 1986
- Endocrine effects of danazol in the treatment of endometriosis 1984
- Effects of danazol on gonadal steroidogenesis in patients with a complete form of testicular feminization 1982
- Structural and Functional Regression of Polycystic Ovaries by Danazol 1981
- Transient Adrenogenital Syndrome due to Exposure to Danazol in Utero 1981
- Androgen uptake in the female reproductive system of a nonhuman primate 1981
- Actions of danazol in vivo on cytochrome P-450 and steroidogenic enzymes in rat testis and liver microsomal preparations 1981
- Danazol inhibits human adrenal 21-and 11β-hydroxylation invitro 1980
- Danazol Suppresses Luteal Function in Vitro and in Vivo 1980
- Pharmacology and Pharmacokinetics of Danazol 1980
- Evidence that danazol inhibits gonadotropin-induced ovarian steroidogenesis at a point distal to gonadotropin-receptor interaction and adenosine 3′,5′ cyclic monophosphate formation 1980
- Inhibition of Adrenal Steroidogenesis by Danazol in Vivo 1980
- Mechanism of induction of luteal phase defects by danazol 1980
- The “Treatment” of Unexplained Infertility with Danazol 1979
- Effect of danazol on estradiol-17β and progesterone secretion by porcine ovarian cells in vitro 1979
- Danazol Binding to Rat Androgen, Glucocorticoid, Progesterone, and Estrogen Receptors: Correlation With Biologic Activity 1979
- Increased Accumulation of Estrogen Receptors in Pituitary Nuclei of Danazol Treated Rats 1979
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- last seen: 2026-05-10T10:42:17.238252+00:00
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