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''-pentachlorobiphenyl (PenCB), 2,3,7,8-tetrachloro (TCDF) and 2,3,4,7,8-pentachlorodibenzofuran (PenCDF), which are potent 3-methylcholanthrene(MC)-type inducers, increased selectively 7.alpha.-hydroxylation but strongly suppressed 2.alpha.-, 6.beta.- and 16.alpha.-hydroxylations as well as 5.alpha.-reduction of 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 with their toxic potency. This kind of change was shown by pretreatments not only with MC itself but also the phenobarbital-type (2,4,5,2'',4'',5''-hexachlorobiphenyl) and the mixed type PCB [polychlorinated biphenyl] (Kanechlor 400, a PCB mixture with 48% Cl 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. Either 2,3,7,8-TCDF or 2,3,4,7,8-PenCDF gave similar metabolic pattern; their residual levels in the liver were greatly different from each other at the time of sacrifice. The change of the steroid metabolism produced by highly toxic PCB and PCDF [polychlorinated dibenzofuran] may be responsible, at least in part, for the endocrine symptoms caused by these compounds via disturbance of steroid homeostasis.