Abstract
To explore the control of thyroid hormone metabolism in brain during maturation, we have measured iodothyronine deiodination in homogenates of rat cerebrum, cerebellum, and hypothalamus from 1 d postnatally through adulthood. Homogenates were incubated with (125)I-l-thyroxine (T(4)) + [(131)I]3,5,3'-l-triiodothyronine (T(3)) + 100 mM dithiothreitol. Nonradioactive T(4), T(3), and 3,3',5'-triiodothyronine (rT(3)) were included, as appropriate. The net production rate of [(125)I]T(3) from T(4) in 1-d cerebral homogenates was similar to the rate in adult cerebral homogenates (9.9+/-2.5[SEM]% vs. 8.9+/-1.2% T(4) to T(3) conversion in 2 h). Production of T(3) was not detectable in 1-d cerebellar and hypothalamic homogenates. The net T(3) production rate in adult cerebellar homogenates was twice as great as, and that in adult hypothalamic homogenates similar to, the rate in cerebral homogenates. Tyrosyl ring deiodination rates of T(4) and T(3) were more than three times as great in cerebral homogenates from 1-d-old rats as in adult cerebral homogenates. In cerebellar homogenates from 1-d-old rats, tyrosyl ring deiodination rates were much greater than the rates in adult cerebellar homogenates, but less than those in 1-d cerebral homogenates. In 1-d hypothalamic homogenates, tyrosyl ring deiodination rates were the highest of all the tissues tested, whereas rates in adult hypothalamic homogenates were similar to those in adult cerebral homogenates. During maturation, T(4) 5'-deiodination rates increased after 7 d and exceeded adult rates between 14 and 35 d in cerebral and cerebellar homogenates, and at 28 and 35 d in hypothalamic homogenates. In cerebral homogenates, the peak in reaction rate at 28 d reflected an increase in the maximum enzyme activity (V(max)) of the reaction. T(4) and T(3) tyrosyl ring deiodination rates decreased progressively with age down to adult rates, which were attained at 14 d for cerebrum and cerebellum and at 28 d for hypothalamus. These studies demonstrate quantitative differences in T(4) 5'-deiodinase activities in cerebrum, cerebellum, and hypothalamus at all ages, with the overall maturational pattern differing from the developmental patterns of both the pituitary and hepatic T(4) 5'-deiodinases. Iodothyronine tyrosyl ring deiodinase activities also vary quantitatively among these same brain regions and exhibit a pattern and a time-course of maturation different from that of the T(4) 5'-deiodinase. These enzymes could have important roles in the regulation of intracellular T(3) concentrations and, hence, on the expression of thyroid hormone effects.