New approaches to thyroid hormones and purinergic signaling

Abstract

It is known that thyroid hormones influence a wide variety of events at the molecular, cellular, and functional levels. Thyroid hormones (TH) play pivotal roles in growth, cell proliferation, differentiation, apoptosis, development, and metabolic homeostasis via thyroid hormone receptors (TRs) by controlling the expression of TR target genes. Most of these effects result in pathological and physiological events and are already well described in the literature. Even so, many recent studies have been devoted to bringing new information on problems in controlling the synthesis and release of these hormones and to elucidating mechanisms of the action of these hormones unconventionally. The purinergic system was recently linked to thyroid diseases, including enzymes, receptors, and enzyme products related to neurotransmitter release, nociception, behavior, and other vascular systems. Thus, throughout this text we intend to relate the relationship between the TH in physiological and pathological situations with the purinergic signaling.

Figure 1

Schematic figure representing our data relating the purinergic system with hyperthyroidism in the CNS. The figure demonstrates that the induction of hyperthyroidism resulted in a significant reduction in the NTPDases and 5′-nucleotidase (5′-NUC) activities which degrade the ATP to adenosine in the brain rats chronically treated with T4 [55]. This result was also observed in 5′-nucleotidase expression in brain of hyperthyroid rats [57]. This leads to an increase of ATP availability as an excitatory neurotransmitter and the reduction of adenosine as an inhibitory neuromodulator in different brain fractions studied. The reduction in the extracellular adenosine levels may reduce the inhibitory effects mediated by adenosine A1 receptors. This relation was demonstrated in hyperthyroidism, once that N6-cyclopentyladenosine (CPA), a selective agonist of the A1 adenosine receptor, reverted the hyperalgesia induced by hyperthyroidism and increased the total antioxidant reactivity in hyperthyroid brain [58]. Moreover, the effects observed in the nervous system were also observed in blood serum of hyperthyroid rats, indicating a possible use of soluble enzyme markers for this thyroid disease [55, 59].