The effect of some antiprostatic steroids upon cortisol production by guinea-pig adrenal cells stimulated by ACTH.
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.
Robertson
W R
WR
Department of Chemical Pathology, University of Manchester, Hope Hospital, Salford, U.K.
Lambert
A
A
Mitchell
R
R
Kendle
K
K
Petrow
V
V
D015096:3-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors; D000311:Adrenal Glands / Q000187:drug effects* / Q000201:enzymology; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000726:Androgen Antagonists / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006854:Hydrocortisone / Q000096:biosynthesis*; D008552:Melengestrol Acetate / Q000494:pharmacology*; D011245:Pregnadienes / Q000494:pharmacology*; D011374:Progesterone / Q000031:analogs & derivatives* / Q000494:pharmacology
D000726:Androgen Antagonists; D011245:Pregnadienes; C036790:6-methylene-4-pregnene-3,20-dione; D011374:Progesterone; D008552:Melengestrol Acetate; C062007:17-acetoxy-6,16-dimethylene-4-pregnene-3,20-dione; D000324:Adrenocorticotropic Hormone; D015096:3-Hydroxysteroid Dehydrogenases; D006854:Hydrocortisone