During adult-onset peripheral hypothyroidism, the brain maintains normal levels of thyroid hormone for some time through a mechanism of ‘central homeostasis’. Although onset, duration, and termination of such a homeostatic phenomenon have been recently evaluated in rat models, the mechanism behind remains unknown. During our investigation to understand the mechanism further, we injected the protein synthesis blockers actinomycin D and cycloheximide along with propylthiouracil to adult male rats during the days of onset (day 2) and termination (day 20) of the homeostatic mechanism. We evaluated synaptosomal T3 level and neuronal Na+-K+-ATPase and acetylcholinesterase activities along with deiodinase II activity and cyclic adenosine monophosphate level in the cerebral cortex. The results indicated prevalence of unchanged or lower levels of synaptosomal T3 on the 2nd and on the 20th day, respectively. Such a condition has been parallely supported by reflections in cerebrocortical deiodinase II activity and cyclic adenosine monophosphate levels. The activities of cerebrocortical synaptosomal Na+-K+-ATPase and acetylcholinesterase, which are the two important physiological parameters for neuronal function, have been found to be supportive of the involvement of a neuronal protein-mediated factor in the ‘on’ and ‘off’ reactions in central homeostasis during peripheral hypothyroidism. The results of our study indicate that the expression of ‘central thyroid hormone homeostasis’ is a genomic nuclear-mediated mechanism.
Background: Imbalance in thyroid hormone concentrations has been linked with profound neurobehavioral alterations in the adult. Peripheral hypothyroidism is associated with a phenomenon of central thyroid hormone homeostasis in adult rat. This central homeostasis mechanism could be maintained by adrenergic interplay due to close physiological association between sympathetic nervous system activity and thyroid hormones. The central homeostasis is characterized by increased cerebrocortical synaptosomal T3 content, deiodinase type II (DII) activity, and cAMP content. Methods: We injected specific α- and β-adrenergic receptor (AR) agonists and antagonists along with an anti-thyroid drug to find out any AR-mediated action on central homeostasis. Results: The α2-AR agonist did not alter the onset of central homeostasis, but prolonged its duration. Similar prolongation was observed with α2-AR antagonist and β-AR agonist, but these compounds amplified the normal anti-thyroid drug-induced rise in cerebrocortical T3 content on the day of onset of central homeostasis. Injections of the β-AR antagonist did not cause any perturbations. All these observations have been supported by parallel changes in cerebrocortical DII activity, cAMP and [Ca2+]i content. Conclusion: There emerges a close correlation between cerebral T3 content, DII activity, cAMP and [Ca2+]i content that are regulated by the AR system. Thus, thyroid hormone homeostasis in the adult mammalian brain is maintained primarily by the β-adrenergic pathway along with an unexpected pharmacological involvement of the α-ARs.
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