Nature of the enhancement of hepatic uridine diphosphate glucuronyltransferase activity by 2,3,7,8-tetrachlorodibenzo-p-dioxin in rats

After single low-level oral doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to rats, hepatic microsomal p-nitrophenol (PNP) glucuronyltransferase activity was elevated approximately 6-fold, whereas the hepatic glucuronyltransferase conjugating testosterone or estrone was unaffected. Solubilized and purified PNP glucuronyltransferase and steroid glucuronyltransferases from control and TCDD-treated rats exhibited the same relative activities (TCDD:control) as when the enzymes were bound to the endoplasmic reticulum. Elevation of PNP glucuronyltransferase was still evident 73 days after a single oral dose of 25 μg TCDD/kg. Female rats were more susceptible to TCDD actions on liver microsomal PNP glucuronyltransferase than males. The effects of TCDD treatment on PNP glucuronyltransferase appeared to be related to increased amounts of liver enzyme for the following reasons: (1) K_m values for PNP and UDPGA were unchanged by TCDD treatments; (2) the magnitude of the TCDD-induced increase of PNP glucuronyltransferase activity was the same whether enzyme activity was measured in the presence or absence of Mg²⁺ or Triton X-100; (3) TCDD, when added in in vitro, had no detectable effect on enzyme activity; (4) TCDD treatment of rats did not change total hepatic microsomal phospholipid or cholesterol contents: (5) pH optima were unaffected by TCDD treatment; (6) solubilization of enzyme was not accompanied by a change in the TCDD induction effect: and (7) actinomycin D appeared to block the initial phase of induction.