Effects of LiCl on triiodothyronine (T3) binding to nuclei from rat cerebral hemispheres

The therapeutic effects of lithium in mania and depression are thought to be mediated by its effects on plasma thyroid hormone (T4, T3) levels. Inasmuch as T3 affects transcription by binding with its nuclear receptors, in this study we examined whether Li+ alters T3 nuclear binding. Although plasma T3 and T4 levels were not affected, 125I-T3 uptake was decreased, and both in vivo and in vitro studies showed a significant increase in nuclear T3 binding in brain and liver tissue. This increase was shown to reflect an increase in maximal binding density. On the basis of these findings, it is proposed that Li+ exerts its action by inducing "cellular hypothyroidism." Integrating existing information on thyroid hormones and affective diseases and the effects of hypothyroidism on neurotransmitters thought to be altered in mania and depression, this hypothesis is supported and contributes to understanding of the effects of LiCl and thyroid hormones in affective diseases.