Phenolic and tyrosyl ring iodothyronine deiodination and thyroid hormone concentrations in the human central nervous system

In the present study we investigated the biochemical properties of in vitro phenolic (5'D) and tyrosyl (5D) ring deiodination and the tissue concentrations of T-4, T-3, and rT(3) in adult human central nervous system (CNS) tissue. All samples were obtained from nontumoral tissue at autopsy (n = 6) or neurosurgical operation (n = 5). Both phenolic and tyrosyl ring deiodinase activities were demonstrable in all samples obtained intraoperatively, whereas only tyrosyl ring deiodination was evident in the tissues obtained postmortem. The phenolic ring deiodination pathway corresponded to the type II 5'-deiodinase isoenzyme with regard to its high affinity for T-4 and rT(3) (K-m = 2.2 and 2.4 nmol/L, respectively), its insensitivity to 6-propyln-2-thiouracil (PTU), and the sequential reaction mechanism. No PTU-sensitive 5'-deiodination of rT(3) was demonstrable. Tyrosyl ring deiodination of both T-4 and T-3, showed typical type III 5D kinetics (K-a, 6.5 nmol/L for T-4 and 3.4 nmol/L for T-3) and was PTU insensitive. Nanomolar concentrations of tissue T-4, T-3, and rT(3) were detected in samples obtained both intraoperatively and postmortem. They were very similar to the absolute values of the apparent K-m for T-4, T-3, and rT(3) in the phenolic and tyrosyl ring deiodination pathways. In conclusion, we have demonstrated the coexistence of both phenolic and tyrosyl ring deiodinase activities in the human CNS. Their kinetic characteristics, substrate specificity, and reaction mechanisms are very similar to the corresponding type II 5'- and type III 5-iodothyronine deiodinase activities in rat brain. In contrast to the findings in the rat CNS, no PTU-sensitive phenolic ring deiodinase (i.e. type I 5'D) activity was found in the human CNS. This may explain the relatively high tissue concentrations of rT(3).