HYDROCORTISONE AND SOME OF ITS EFFECTS ON INTERMEDIARY METABOLISM I. IN VIVO STUDIES

Abstract

In this report, it has been demonstrated that hydrocrotisone, shortly after injection to fasted adrenalectomized rats, markedly decreased the rate of oxidation of glucose and glycerol, increased their rates of conversion to liver glycogen, and increased the oxidation of palmitate-1-C¹⁴. Hydrocortisone had equivocal effects on the oxidation rate of acetate and pyruvate; injection of unlabeled pyruvate in the presence of hydrocortisone produced increased blood levels of substrate. Hydrocortisone did not affect the oxidation of amino acids under the conditions used in these experiments. Injection of hydrocortisone, subcutaneously and via the saphenous and portal veins, led to glycogenic effects which are interpreted to mean that the steroid was acting primarily on tissues other than the liver. Additional experiments concerning the time course of both muscle and liver glycogen synthesis after glucose injection suggests that hydrocortisone decreases the rate of oxidation of glucose at some level below that of glucose entry or transport into the cell. Of administered amino acids, fat, protein, lactate and glucose, only the latter two substrates markedly influenced the glycogenic response to hydrocortisone. These data are consistent with the hypothesis that hydrocortisone is primarily concerned with the disposition and metabolism of glucose or one of its immediate metabolites. Administration of hydrocortisone to fasted adrenalectomized rats led to early increases in the plasma levels of lactate and glucose; amino acid, nonesterified fatty acid, and protein levels were not significantly altered. The rapid rise in blood glucose levels is postulated as due to the inhibitory effects of hydrocortisone on glucose metabolism in “peripheral” tissues; not a reflection of a primary effect on “gluconeogenesis” or conversion of non-carbohydrate precursors to glucose. Additional evidence supporting the above conclusions is also presented.