A Unique Change of Steroid Metabolism in Rat Liver Microsomes Induced with Highly Toxic Polychlorinated Biphenyl(Pcb) and Polychlorinated Dibenzofuran(Pcdf)

Abstract

Pretreatments of rats with the highly toxic compounds such as 3,4,5,3',4'-pen-tachlorobiphenyl(PenCB), and 2,3,7,8-tetrachloro(TCDF) and 2,3,4,7,8-pen-tachlorodibenzofuran(PenCDF), which are potent 3-methylcholanthrene(MC)-type inducers, increased selectively 7a-hydroxylation, but strongly suppressed 2α-, 6β- and 16α-hydroxyla-tions as well as 5α:-reduction or progesterone and testosterone in the liver microsomes. This unique change in the metabolic pattern was accompanied by a marked decrease in total metabolism of both steroids and appeared to correlate apparently with their toxic potency. This kind of change was not shown by pretreatments with not only MC itself but also the phenobarbital-type(2,4,5,2',4',5-hexachlorobiphenyl) and the mixed type PCBs(Kanechlor 400, a PCB mixture with 48% chlorine content), all of which possess only a low acute toxicity. The metabolic change produced by 3,4,5,3',4'-PenCB, 2,3,7,8-TCDF and 2,3,4,7,8-PenCDF might not be due to their stimulatory or inhibitory effects, because when added to the incubation mixture 3,4,5,3',4'-PenCB did not change the metabolic pattern with MC-microsomes to that with 3,4,5,3',4'-PenCB-microsomes. Furthermore, either 2,3,7,8-TCDF or 2,3,4,7,8-PenCDF gave similar metabolic pattern whereas their xesidual levels in the liver were greatly different from each other at the time of sacrifice. These results suggest that this kind of unique change of the steroid metabolism produced by highly toxic PCBs and PCDFs may be responsible, at least in part, for the endocrine symptoms caused by these compounds via disturbance of steroid homeostasis. © 1982, The Pharmaceutical Society of Japan. All rights reserved.