THE EFFECTS OF AN INTERFERON INDUCER, POLYRIBOINOSINIC POLYRIBOCYTIDYLIC ACID ON CYTOCHROME-P-450 DEPENDENT HEPATIC PROGESTERONE METABOLISM

A time course study on the effects of an interferon inducing agent, polyriboinosinic polyribocytidylic acid (poly rIrC) on the hepatic cytochrome P-450 dependent progesterone metabolism was performed. Administration of a single dose of poly rIrC (10 mg/kg i.p.) to adult male Wistar rats caused a time dependent effect on liver weight, microsomal protein and total cytochrome P-450 levels, as well as the 16alpha and 6beta hydroxylation of progesterone. The response was multiphasic, with a maximal depression of both hydroxylase activity 48 hours post-injection, followed by enhanced activity at 72 hours and subsequent return to control activity twenty-four hours later. A second less dramatic rise in the activities followed, bringing the 16alpha and 6beta hydroxylase activity to 159% and 141% of their respective control values by 336 hours, at which point of time, the trend appeared to be still on the rise. The enhanced activity at 72 hours was preceded by an increase in serum cortisol and corticosterone levels, the ability of which to enhance the activity of 6beta hydroxylation of steroids may partly explain the phenomenon.