Oxidative Phosphorylation in Liver Mitochondria from Adrenalectomized Rats and the Response to Hormones Added in Vitro.

In recent years there has been an increasing tendency to determine the intracellular action of hormones. Many hormones are known to have an effect on carbohydrate metabolism in general and on carbohydrate oxidation and adenosine triphosphate synthesis in particular. Previous work in this laboratory has shown that the efficiency of oxidative phosphorylation is depressed in insulin-deficient animals (1) and in hypophysectomized animals (2). In both cases insulin in vitro is effective in restoring P :0 ratios. Some of the adrenocortical steroids and epinephrine also affect carbohydrate metabolism. Lack of adrenocortical steroids renders animals extremely sensitive to shock, one aspect of which is an inability to mobilize energy reserves. Thus adrenal hormones may play a vital role in tissue respiration and phosphorylation. There have been several investigations of the metabolic effect of adrenal steroids on metabolism with the use of tissue homogenates and tissue slices. These have been reviewed by Gordon, Beutinck, and Eisenberg (3), Hayano and Dorfman (4), and Umbreit (5). More recently, metabolic regulation by hormones has been summarized by Randle (6). One of the most prevalent views is that steroids inhibit oxidation at the dehydrogenase level. However, Albaum, Hirshfield, Touhazy, and Umbreit (7) found that neither adrenalectomy nor cortisone treatment had any effect upon the ability of the tissue homogenates to synthesize adenosine triphosphate. More recently Gallagher (8) has reported that hydrocortisone in vitro specifically inhibits the oxidation of substrates which require pyridine nucleotides for electron transport in liver mitochondria. He maintains that this is due to a progressive increase in the permeability of the mitochondrial membrane and a concomitant loss of soluble cofactors. Kerppola (9) has reported that prolonged injection of cortisone in vivo often produces some inhibition of oxidative phosphorylation but these results varied considerably with the substrate used, and with the sex and age of the animals. He also suggested (10) that. cortisone inhibits respiration at the level of cytochrome oxidase. Ulrich (11) has reported that