A B S T R A C T Our recent in vivo studies have suggested that intrapituitary L-thyroxine (T4) to 3,5,3'-triiodo-L-thyronine (T3) conversion with subsequent nuclear binding of T3 is an important pathway by which circulating T4 R. In fasted rats, neither N:M ratio was depressed, although hepatic T4 to T3 conversion in the same animals was 50% of control (P < 0.005). lopanoic acid (13 ,uM), but not 6-n-propylthiouracil (29 MM), decreased the N:M ['251]T3 with a significant decrease in the value for R (P < 0.025 or less). Neither sodium iodide (6 ,uM) nor thyrotropin-releasing hormone (7-700 nM) affected the T3 N:M ratios. These results indicate that intrapituitary T4 to T3 conversion is stimulated in hypothyroidism and depressed in T4-treated animals, whereas opposite changes occur in hepatic T4-5'-monodeiodination. Unlike liver, anterior pituitary T4-5'-monodeiodination is not affected by fasting or incubation with 6-n-propyl-2-thiouracil, but T4 to T3 conversion is inhibited in both by iopanoic acid. These results indicate that there are important differences between anterior pituitary and other tissues in the regulation of T4-5'-monodeiodination.

T4-5'-monodeiodination in pituitary fragments and liver homogenates, serum thyroid hormones, an index of serum thyroid hormone protein binding, and serum TSH were measured in rats aged 2-72 days. Serum T4, T3, and TSH concentrations were lower in the 2-, 4-, and 9-day-old rats than in adult rats. The serum thyroid hormone-binding index was highest in neonatal rats, fell to a nadir at 21 days, and rose thereafter. The intrapituitary T4-5'-monodeiodination rate was 3.5 times the 72-day value in 2- and 4-day-old rats and fell to the 72-day value by 30 days of age. T4-5'-monodeiodination rates in liver homogenates were lower than the adult values in 2-, 4-, and 9-day-old rats, reaching the adult value in 21-day-old rats. When 5 mM dithiothreitol were included in the liver homogenate incubations, the absolute T4-5'-monodeiodination rates were increased, and the differences among 2-, 4-, 9-, 21-, and 72-day-old rats were abolished. Increased rates of intrapituitary T4-5'-monodeiodination may, in part, account for lower serum TSH concentrations in neonatal rats than in adults despite the lower serum T4 concentrations in the former. The differences between changes in pituitary and liver T4-5'-monodeiodination during maturation provide further evidence for local rather than systemic regulation of this reaction.

No abstract