Thyroid Hormone Homeostasis in Brain: Possible Involvement of Adrenergic Phenomenon in Adult Rat

Abstract

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.

“Quo Vadis?” Deciphering the Code of Nongenomic Action of Thyroid Hormones in Mature Mammalian Brain

“…Stimulated levels of D-II have been described during hypothyroidism. This supports the first initial report [13] of elevation of brain L-T3 levels during n-propylthiouracil (PTU)-induced hypothyroid conditions [14,15,32]. In brain, approximately 80% of the L-T3 is produced locally from L-T4 by D-II.…”

“…Expression of D-II is an important protective mechanism against hypothyroidism. This prevalence of TH homeostasis is a preventive measure and thought to be neuroprotective [1,[13][14][15][16].…”

Possible Influence of Dopaminergic Receptor in Maintenance of Thyroid Hormone Homeostasis: A Study in Adult Rat Brain

“…The involvement of adrenergic receptors in the maintenance of 'central thyroid hormone homeostasis' has already been established [25]. The present study indicates a possible role of another class of catecholaminergic compounds, the dopamines, in the mediation of 'central thyroid hormone homeostasis'.…”

Revisiting Thyroid Hormones in Schizophrenia

“…The increased dopaminergic activity was hypothesized to affect the pituitary secretory function, and decreased beta-adrenergic activity was inferred as consequence of decreased serum TSH concentration. This is of further interest as α 1- and β -adrenergic catecholamines are involved in maintaining deiodinase activity, and thus brain thyroid status [80]. As such, type-1 deiodinase impairment may result in a drop in T 3 levels, with unchanged T 4 , and type 2 or 3 deiodinase impairment may be reflected in decreased T 4 metabolization.…”