Maintenance of Homeostasis for Thyroid Hormone in the Adult Rat Brain: Possible Involvement of a Nuclear-Mediated Phenomenon

Abstract

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.

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

“…Thus, increase in DII activity on the 2nd day of PTU treatment (Day '2') pointed to an adaptive increase in response to PTU-induced peripheral hypothyroidism to maintain the neural T3 content [8]. Again, the fall in DII activity after twenty days of continuous PTU injections (Day '20') provide the reason for lower synaptosomal T3 content and disruption of 'central thyroid hormone homeostasis' in our experimental system [8]. The DII activity after treatment with the BROMO was found to be at the control level both during the onset (Day '2') and termination (Day '20') of 'central thyroid hormone homeostasis'.…”

“…In astrocytes, cAMP stimulation is required to express DII activity [20]. There has been a significant rise in the cerebrocortical cAMP content on the day of onset of the 'central thyroid hormone homeostasis' (Day '2'), which accounted for the increase in the activity of DII and subsequent rise in brain T3 level [8]. Similarly, the fall in cAMP level on Day '20' has been accompanied by a corresponding lower cerebral DII activity and T3 content [8].…”

“…There has been a significant rise in the cerebrocortical cAMP content on the day of onset of the 'central thyroid hormone homeostasis' (Day '2'), which accounted for the increase in the activity of DII and subsequent rise in brain T3 level [8]. Similarly, the fall in cAMP level on Day '20' has been accompanied by a corresponding lower cerebral DII activity and T3 content [8]. BROMO and HALO showed opposite levels of cAMP when they were injected either alone, or along with PTU during the days of onset and termination of central homeostasis.…”

“…The 5'-deiodinase type II (DII) activity has been measured according to the method of Kodding et al [9] with slight modifications [8], using a substrate solution of 0.1 M TrisHCl buffer (pH 7.4), 3 mM EDTA, 150 mM dithioerythritol, 0.4 μM T4 and 100 -150 μg brain tissue protein. The T3 formed under such conditions after incubation were estimated by ELISA.…”

“…The cyclic AMP (cAMP) content has been assayed by competitive enzyme immunoassay, as described before [8] using a cAMP EIA kit from Cayman Chemical Co., USA. The plates were read at a wavelength between 405 and 420 nm in ELISA reader.…”