Thyroid hormone metabolism and the source of plasma triiodothyronine in 2-week-old rats: effects of thyroid status.

Earlier studies have shown larger increments in serum T3 in 2-week-old congenitally hypothyroid rats than in euthyroid controls after injections of small doses of T4. Since hepatic and renal 5'-deiodination of T4 to T3 in vitro (5' D-I) is reduced during the neonatal period and in hypothyroidism, those results suggest that there may be major changes in the distribution and metabolism of T3 or that an alternative enzymatic pathway is the predominant source of extrathyroidally produced T3 in these rats. The alternative pathway, 5' D-II, is a relatively minor source of serum T3 in adult euthyroid rats, but the contribution of this pathway to the extrathyroid T3 pool during the neonatal period and in hypothyroxinemia is not known. Consequently, we studied [125I]T4 and [131I]T3 kinetics and fractional T4 to T3 conversion in 2-week-old euthyroid and hypothyroid rats and then explored the source of circulating T3 by manipulating 5' D-I activity with propylthiouracil and that of 5' D-II with thyroid hormone. The plasma clearance rate of T4 was increased in hypothyroid rats, a difference entirely accounted for by the faster fractional rate of irreversible removal in the hypothyroid pups. Plasma clearance rate of T3 was reduced in hypothyroid rats owing to the reduced volume of distribution of T3. Fractional T4 to T3 conversion was 2- to 3-fold higher in euthyroid or hypothyroid neonates than in adult rats. In euthyroid rats the serum concentration of T4 was 36 +/- 1 (SEM) ng/ml and that of T3 0.61 +/- 0.03 ng/ml, and the production rates were 432 and 159 ng day-1 30 g-1 BW for T4 and T3, respectively. About 80% of the T3 in euthyroid neonates was produced extrathyroidally . These findings are inconsistent with hepatic and renal 5' D-I being the main source of serum T3 in 2-week-old rats. In fact, liver and kidney 5' D-I activities were 40% and 65% of the corresponding adult values in euthyroid neonates, and in hypothyroid pups were further reduced to 15% and 17%. In contrast, 5' D-II, previously reported to be high in central nervous tissue and pituitary, was 7-10-fold higher in brown adipose tissue (BAT) of hypothyroid pups than in that of euthyroid ones.(ABSTRACT TRUNCATED AT 400 WORDS)