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- W2143149830 abstract "ABSTRACT Rat adrenal mitochondrial preparations supplemented with an NADPH-generating system were incubated with various labelled substrates in order to evaluate further the action of metyrapone on the utilization of cholesterol for steroid biosynthesis 1 ). The formation of pregnenolone from [4- 14 C] cholesterol (0.5, 1.0 and 2.0 μCi) in 5, 10 and 15 min incubations was decreased by 72–82 % in the presence of metyrapone (0.5 m m ). Similarly, the generation of labelled side chain fragments from [26- 14 C]-cholesterol was depressed 36–42 % by 0.2 m m metyrapone and 65–70 % by 1.0 m m inhibitor during 30, 60 and 90 min incubations. Metyrapone inhibition of the side chain cleavage was not observed, however, if cholesterol was replaced as substrate by its C-20 hydroxylated analog: The formation of pregnenolone from [7- 3 H]20α-hydroxycholesterol (0.5, 1.0 and 2.0 μCi), also an NADPH-mediated mitochondrial reaction, was not affected by similar concentrations of metyrapone, indicating that the inhibition observed with cholesterol as substrate is not related to non-specific toxic effects, to interference with NADPH generation or to impairment of NADPH function in the mitochondrial electron transport system. Parallel incubations with [4- 14 C] 11-deoxycorticosterone and with [4- 14 C] cholesterol over a wide range of inhibitor concentrations (0.01–1.0 m m ) demonstrated that the effects of metyrapone on 11β-hydroxylation and on the side chain cleavage were dose-related; at low concentrations, however, metyrapone was a more potent inhibitor of 11β-hydroxylation than of cholesterol conversion to pregnenolone. These studies demonstrate clearly in the rat adrenal the dual inhibitory effect of metyrapone sug-gested by previous in vivo and in vitro observations in man." @default.
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- W2143149830 date "1974-08-01" @default.
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- W2143149830 title "SITES OF METYRAPONE INHIBITION OF STEROID BIOSYNTHESIS BY RAT ADRENAL MITOCHONDRIA" @default.
- W2143149830 doi "https://doi.org/10.1530/acta.0.0760703" @default.
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