L-triiodothyronine: Is this peripheral hormone a central neurotransmitter?

Abstract

Ltriothyronine (T3) has previously been shown to chonce fast-phase, depolarization-induced45Ca uptake3H-gmma-aminobutyric acid release by rat specptomes at low nanomolar concentrations suparable to those reported for whole brain. Secertheless, the physiologic importance of these rmclear-mediated effects of T3 has remained uncertain, apri because specific mechanisms and the presence of fill presumptive sites of action have not been trated. Isotopic studies showing that L-tetraiodothyronine abfroxine, T4 and T3 are concentrated in synaptosomes, that T4 is deiodinated to T3 suggested that sed the gaious levels of T3 in nerve terminals are probably much higher than in other compartments of the brain. In the present study we confirmed that endogenous levels of T3 in nerve terminals are at least eightfold higher, and may be as much as 60-fold higher, than in whole brain. More importantly, we showed that both 125I-labeled T3 and endogenous T3, but not 125I-T4 or endogenous T4, are released from depolarized synaptosomes, primarily by a Ca2+-dependent process. This demonstrates a mechanism for raising the level of T3 within the synapse, where the hormone may interact with preand postsynaptic binding (or uptake) sites, and suggests that the peripheral hormone T3 may be a neurotransmitter. © 1993 American College of Neuropsychopharmacology.