Abstract
Dispersed guinea-pig adrenal cells have been employed in the in vitro estimation of the biological potency and sites of action of drugs acting against the adrenal. The effect of 12 drugs on cortisol secretion from cells stimulated with adrenocorticotrophin (ACTH, 50 ng/L, a 95% saturating dose) has been tested. All the drugs depressed cortisol output in a dose-related fashion. The concentration of drug which inhibited secretion by 50% was (mumol/L, mean +/- SEM): etomidate 0.1 +/- 0.002; epostane 0.44 +/- 0.02: 17-ketotrilostane 0.55 +/- 0.04: trilostane 1.3 +/- 0.1: metyrapone 3.5 +/- 0.6: cyproterone acetate 4.6 +/- 0.2: megestrol acetate 11 +/- 2: danazol 22 +/- 2: aminoglutethimide 41 +/- 5: stanozolol 50 +/- 4: thiopentone 160 +/- 18: propofol 170 +/- 18. The sites of the anti-steroidogenic effect of seven of these drugs have also been established using a method based upon the sequential stimulation by the exogenous precursor steroids of the various steps leading to the biosynthesis of cortisol by adrenal cells. Propofol acts between ACTH binding and pregnenolone production, trilostane, megestrol acetate and cyproterone acetate are 3 beta-hydroxysteroid dehydrogenase inhibitors whereas metyrapone, etomidate and thiopentone act at 11 beta-hydroxylase.
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