EFFECTS OF CHRONIC EXPOSURE TO PCBS ON CYTOCHROME-P450 SYSTEMS AND STEROIDOGENESIS IN LIVER AND TESTIS OF BULLS (BOS-TAURUS)

Effects of chronic exposure to PCBs on the microsomal cytochrome P450 (CYP) enzymes in liver and testis of bulls (Bos taurus) were determine d by comparing the constitutive and PCB-induced alkoxyresorufin O-deal kylase and testosterone hydroxylase activities. Specific inductions of the prevailing hepatic ethoxyresorufin O-deethylation and 6 beta-hydr oxylation of testosterone are suggestive of the induction of CYP1A1 an d CYP3A-like enzymes by PCBs. A high level of PCB-inducible androstene dione formation was also found. The hepatic CYP2B activities (i.e. pen toxyresorufin O-depentylase and testosterone 16 beta-hydroxylase) and CYP2C11-like testosterone 2 alpha-hydroxylase were increased only weak ly, The testicular microsomal CYP activities were non-specifically red uced by the PCB exposure, except for the androstenedione formation and 16 beta-hydroxylation of testosterone. The inhibition of the activity of mitochondrial CYP11A, as the rate-limiting enzyme of steroidogenes is measured with resorufin 3 beta-hydroxy-22,23-bisnor-5-cholenyl ethe r as the fluorogenic substrate, exceeded 50% in testes of the PCB-cont aminated bulls. The latter activity as well as the hepatic testosteron e 6 beta-hydroxylation and hepatic and testicular androstenedione form ation may significantly contribute to the decrease in testosterone lev els after the PCB intake. (C) 1998 Elsevier Science Inc. All rights re served.