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  • Title: The effect of some antiprostatic steroids upon cortisol production by guinea-pig adrenal cells stimulated by ACTH.
    Author: Robertson WR, Lambert A, Mitchell R, Kendle K, Petrow V.
    Journal: Biochem Pharmacol; 1989 Nov 01; 38(21):3669-71. PubMed ID: 2557025.
    Abstract:
    The antiprostatic steroids 6-methylene-4-pregnene-3,20-dione (6-MP) (I), 17-alpha-acetoxy-6, 16-dimethylene-4-pregnene-3,20-dione (II), and melengestrol acetate (MGA) (III) were incubated with guinea-pig adrenal cells, both alone and maximally stimulated with ACTH. Cortisol output was then measured by RIA. Increased cortisol-like secretion was obtained with 6-MP in the absence of ACTH. In the presence of ACTH, cortisol-like steroid secretion was the sum of that seen with ACTH and 6-MP alone. It follows that 6-MP stimulates in vitro a cortisol-like steroid cross reacting with the cortisol antibody by a mechanism that by-passes ACTH. Steroid (II) weakly inhibited cortisol output. MGA, in contrast, proved to be a strong inhibitor of cortisol output (ID50 of 2.3 mumol/l). Its site of action was established by adding it to adrenal cells incubated with precursor steroids on the cortisol pathway. Conversion of 3 beta-hydroxysteroids to cortisol was inhibited whereas conversion of 3-keto steroids was not affected. It follows that MGA inhibits 3 beta-hydroxysteroid dehydrogenase.
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