Metyrapone Inhibition of ³H-Hydrocortisone Uptake and Binding in Various Brain Regions of the Pig

Abstract

Metyrapone (MET) inhibition of hydrocortisone (³H-HC) uptake and binding in the cytosol and nucleus of various brain regions of the pig was demonstrated in vivo. The hippocampus, hypothalamus and septum were the regions most sensitive to the inhibition by MET. The hippocampus exhibited the greatest reduction in ³H-HC concentration in whole homogenate, bound in cytosol and in nuclei. The anterior pituitary and cerebral cortex were the least sensitive to MET. In vitro incubation of hypothalami with ³H-HC and MET substantiated the results obtained in vivo with regard to the inhibitory action of MET on ³H-HC uptake and binding. These results were interpreted to indicate that MET may act directly in certain brain regions and that this inhibitory action has important implications for both experimental and clinical uses of this drug.