In vivo interaction of metyrapone with adrenal cortical mitochondrial cytochrome P-450

Metyrapone, a competitive inhibitor of adrenal cortical 11β-hydroxylation, was administered to rats in vivo, and these rats were sacrificed 0.5, 1, 2, 4, 8, and 24 hr later. The in vitro rates of 11β-hydroxylation by adrenal mitochondria were maximally inhibited between 0.5 and 2 hr after metyrapone administration with subsequent recovery at later times. The DOC-induced spectral shift in these same mitochondria was markedly reduced 0.5 hr after metyrapone treatment, but gradual increments were apparent at each succeeding time period studied until control values were again achieved after 24 hr. The metyrapone-induced difference spectra, on the other hand, were markedly and consistently depressed at least until 8 hr after metyrapone administration but had completely recovered by 24 hr. The altered DOC-induced spectral shifts following metyrapone treatment appear to correlate with the activity of the 11β-hydroxylation system.