Enzyme-inhibiting action of hydrocortisone and desoxycorticosterone of mixed function oxidases

Comparative studies have been carried out on the action of two corticosteroids: the mineralocorticoid desoxycorticosterone and the glucocorticoid hydrocortisone, upon single administration in male albino rats, on the hexobarbital sleeping time and the activity of the mixed function oxidases. Applied in equimolar doses, the two steroids prolong the hexobarbital sleeping time, the effect of desoxycorticosterone being stronger. The potentiation of hexobarbital sleeping time by hydrocortisone differs in degree in animals from the different age groups, being most pronounced in mature animals compared with two-week-old immature and old animals. Unlike hydrocortisone, the potentiating effect Of desoxycorticosterone is close in intensity for all age groups studied. Both corticosteroids in single doses (50 mg/kg) inhibit the activity of mixed function oxidases, metabolizing type I substrates--hexobarbital and morphine, the inhibitory effect of desoxycorticosterone being stronger. Hydrocortisone does not influence the metabolism of type II substrates (aniline), while desoxycorticosterone inhibits it considerably. The reasons for the differences observed in the effects of the two compounds are sought in the different involvement of the enzyme systems studied in their metabolism.