Effects of hyper- and hypothyroidism on thyroid hormone concentrations in regions of the rat brain

Abstract

The purpose of this study was to investigate the effects of hyper- and hypothyroidism on thyroid hormone concentrations and deiodinase activities in nine regions of the rat brain. Four weeks of treatment with 75 microg thyroxine (T4)/kg body wt induced a two- to threefold increase in T4 levels in all of these brain regions, whereas the 3,5,3'-triiodothyronine (T3) concentrations were reduced in five brain regions and remained unchanged in four. Even after 8 wk treatment with 300 microg T4/kg, the T3 concentrations remained normal in cortical areas, the hippocampus and amygdala, and were elevated only in areas in which inner-ring deiodinase activity was low or absent, and in the hypothalamus. At the subcellular level, nuclear concentrations of T3 were diminished in hypothyroidism but remained unaltered in hyperthyroidism in all areas except the hypothalamus, where they were enhanced. Cortical mitochondrial succinate dehydrogenase activity was reduced in both hypo- and hyperthyroidism in spite of normal T3 concentrations in hyperthyroid animals. The results show that nuclear T3 concentrations fall in hypothyroidism but do not change during severe hyperthyroidism in any brain region except the hypothalamus. Further research is thus needed to clarify the mechanisms mediating the numerous biochemical and psychological effects of hyperthyroidism.

Effect of Thyroid Function Variations Within the Laboratory Reference Range on Health Status, Mood, and Cognition in Levothyroxine-Treated Subjects

“…thyroid function and health status or mood. Most relevant, ours is the first report that correlates thyroid function in this population with sensitive tests of two cognitive domains, memory and executive function, which map to brain areas known to be responsive to thyroid hormone (30)(31)(32).…”

“…Rather than using less sensitive global screening tests, we employed intensive, sensitive measures that targeted two specific cognitive domains: executive function and memory. Our decision to focus on memory was based on our previous data and other studies suggesting that memory is preferentially affected in subjects with mild thyroid dysfunction (21,29,30), as well as animal studies that support a major role for LT4 in brain areas that mediate memory (31,32). Our decision to focus on executive function was based on the relative lack of information regarding thyroid effects on this cognitive domain, although studies and clinical observations suggest that this critical cognitive process is also affected [reviewed by Samuels (33)].…”

Differences in hypothalamic type 2 deiodinase ubiquitination explain localized sensitivity to thyroxine

“…This in fact has been documented in 2 independent studies. The first shows that systemic infusion of high doses of T4 into hypothyroid animals increases tissue and nuclear T3 in the hypothalamus rather than maintaining normal T3 levels (45). The second shows that a 40% elevation in serum T4, without changes in serum T3, is sufficient to reduce TRH expression by 50% (17).…”

Functional magnetic resource imaging assessment of altered brain function in hypothyroidism during working memory processing

“…It is well accepted that hypothyroidism is related to pathological alterations of thyroid hormone distributions and functioning in both hippocampus and cerebral cortex (1,3,4). There are various adverse effects of hypothyroidism on cerebral-dependent neurocognitive functions (1, 2, 5-7) including working memory (8,9), which is the executive and attentional control of short-term memory providing for temporal storage and online manipulation of information (10).…”