Abstract
The Koritz-Hall hypothesis for the regulation of steroidogenesis by ACTH was analyzed by testing whether it is compatible with experimental data on the dynamic relations between the concentration of ACTH in adrenal arterial blood and cortisol secretion rate. The hypothesis is based on the inhibition of cholesterol hydroxylation by pregnenolone in a mitochondria extract, and proposes that ACTH acts to increase mitochondrial permeability to pregnenolone, thereby lowering intramitochondrial pregnenolone concentration and relieving the inhibition on steroidogenesis. These ideas were incorporated into a dynamic model of steroidogenesis. A search was made for a set of physically realistic kinetic parameters for the model which would permit it to simulate the dynamic responses of the perfused canine adrenal to ACTH. The in vitro data do not show pregnenolone to have a wide enough range of inhibitory action on cholesterol hydroxylation to be compatible with the range over which cortisol secretion rate varies in t...
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