Maturational Patterns of Iodothyronine Phenolic and Tyrosyl Ring Deiodinase Activities in Rat Cerebrum, Cerebellum, and Hypothalamus

Michael M. Kaplan; Kimberlee A. Yaskoski

doi:10.1172/JCI110136

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 ¹²⁵I-l-thyroxine (T₄) + [¹³¹I]3,5,3′-l-triiodothyronine (T₃) + 100 mM dithiothreitol. Nonradioactive T₄, T₃, and 3,3′,5′-triiodothyronine (rT₃) were included, as appropriate. The net production rate of [¹²⁵I]T₃ from T₄ in 1-d cerebral homogenates was similar to the rate in adult cerebral homogenates (9.9±2.5[SEM]% vs. 8.9±1.2% T₄ to T₃ conversion in 2 h). Production of T₃ was not detectable in 1-d cerebellar and hypothalamic homogenates. The net T₃ 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 T₄ and T₃ 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, T₄ 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. T₄ and T₃ 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 T₄ 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 T₄ 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 T₄ 5′-deiodinase. These enzymes could have important roles in the regulation of intracellular T₃ concentrations and, hence, on the expression of thyroid hormone effects.