THE EFFECT OF METHYLCHOLANTHRENE ON BILIARY THYROXINE EXCRETION IN NORMAL AND GUNN RATS

Abstract

SUMMARY Biliary fistulae were produced in rats given [125I]thyroxine (T4) 18 h previously. Treatment of normal animals with 3-methylcholanthrene (MCA) raised the bile: plasma 125I ratio (B: P ratio) and biliary clearance of plasma 125I three times. All of the increase could be explained by enhanced excretion of T4-glucuronide. In Gunn rats the B: P ratio and biliary clearance of plasma 125I was one quarter of normal and only a small fraction of biliary 125I was present as T4-glucuronide. In these animals MCA slightly, but significantly, enhanced the B: P ratio and biliary clearance of plasma radioactivity. The mechanism was not clear; it was not due to increased glucuronide formation and did not appear to be due to effects on the binding of T4 to plasma proteins. MCA, in all the normal rats studied, lowered the serum protein-bound iodine (PBI), but in female Gunn rats it had no effect. Enhanced biliary excretion of T4 seemed to be responsible for the low serum PBI in MCA-treated normal rats. In normal male rats MCA increased thyroid 131I uptake, but had no effect in normal or Gunn female rats. Injection of female mice with MCA reduced the half-life of circulating T4.