Ehanced biliary thyroxine excretion in rats treated with pregnenolone-16alpha-carbonitrile

Normal rats were treated with pregnenolone- 16alpha - carbonitrile (PCN) 10 mg/100 g by stomach tube twice daily for 3 days. In these animals the biliary excretion of intravenously injected 125I-thyroxine (T4) was enhanced and the bile: plasma 125I ratio (B/P ratio) and the biliary clearance rate of plasma 125I-T4 was increased. Normal rats were treated with PCN for 3 days and homozygous Gunn rats for 13 days. In both groups PCN enhanced the bile flow and elevated the B/P ratios and the biliary clearance rate of plasma T4 following ip injection of 125I-T4 17 h previously. PCN-treatment had no effect on the fractions of biliary 125I present as T4-glucuronide, T4 and I- in either the normal or Gunn rats. Treatment with PCN for 10 days produced goitres in normal and Gunn rats and in normal rats elevated the serum TSH (bioassay) levels and the 17 h thyroid 131I uptake as well as the serum PB125I concentrations, without affecting stable PBI concentrations. These data indicated increased pituitary TSH release in response to increased peripheral metabolism of thyroid hormone; enhanced hormonal release from the thyroid kept pace with the accelerated peripheral loss.