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- W2093358301 abstract "Previous reports have shown that 17β-N,N-Diethylcarbamoyl-4-methyl-4-aza-5α-androstan-3-one (4-MA), a synthetic inhibitor of 5α-reductase, exerts an inhibitory effect on 3β-hydroxysteriod dehydrogenase/Δ5−Δ4-isomerase (3β-HSD) activity. To characterize further the effects of 4-MA on steroidogenesis, guinea pig fasciculata-glomerulosa cells in primary culture were treated for 24h with 4-MA. Our data indicate that 4-MA reduced 3β-HSD activity in cultured adrenal cells but had no effect on the activities of 11-hydroxylase, 21-hydroxylase, 17-hydroxylase, and 17,20-lyase. Be decresing the conversion of pregnenolone into progesterone of 17-hydroxypregnenolone into 17-hydroxyprogesterone, 4-MA caused the steroidogenic pathway to shift toward the production of dehydroepiandrosterone. Despite the presence of 4-MA, androstenedione and 11β-hydroxyandrostenedione were produced at levels exceeding the control levels. In the presence of ACTH and 4-MA, corsitol production was inhibited by 90% whereas androstenedione and 11β-hydroxyandrostenediobe were reduced by only 40%. The effect of the compound was reversed by washing the adrenal cells with medium, thus suggesting a direct action of 4-MA on the enzyme itself. In summary, our data indicate that 4-MA markedly reduces the production of cortisol in the adrenals and partially alters the formation of C-19 steroids. It is important to consider this finding in the use of 4-azasteroids in the treatment of prostate cancer, which was previously found to be sensitive to secretion of adrenal C-19 steroids. (Steroids 59: 371–376, 1994)" @default.
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- W2093358301 date "1994-06-01" @default.
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- W2093358301 title "Effects of 4-MA, a potent inhibitor of 5α-reductase, on 3β-hydroxysteroid dehydrogenase/Δ5−Δ4-isomerase activity in guinea pig adrenals" @default.
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- W2093358301 doi "https://doi.org/10.1016/0039-128x(94)90004-3" @default.
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