Thyroid Hormone Levels and Expression of Genes Involved in Regulation of Thyroid System Activity in Male Rats Exposed to Prolonged Low Temperatures, and the Effect of a Thyroid-Stimulating Hormone Receptor Antagonist on These Parameters

Mechanisms of adaptation to prolonged low temperature exposures,aimed at increasing thermogenesis and altering metabolism, includean increase in the activity of the hypothalamic-pituitary-thyroid(HPT) axis. Therefore, it remains a relevant task to explore thebalance of thyroid hormones (THs), expression and activity of enzymesresponsible for their synthesis in the thyroid gland (TG), expressionof the main components of the HPT axis, as well as to investigatethe effect of thyroid stimulating hormone (TSH) receptor antagonistson these indices when administered to animals exposed to cold. Thiswork was aimed to study blood TSH and TH levels and the expressionof hypothalamic, pituitary and thyroid genes involved in their synthesisand secretion in male rats exposed to low temperatures (5°C) for10 days, as well as to assess the effect of a single treatment ofanimals with the thieno[2,3-d]-pyrimidine derivative TPY1, an originalallosteric TSH receptor antagonist, on these indices. Cold-exposedrats developed T3 hyperthyroidism, which was associated with a decreasein the thyroxine level due to an increase in its conversion to T3,as indicated by an increase in the T3/T4 ratio and type 2 deiodinase(DIO2) expression in the TG. Compared to controls, the expressionof thyroidal Tg and Nis genes, encoding thyroglobulinand Na⁺/I^– symporter,increased in the TG of hyperthyroid rats. TPY1 normalized the T3level and decreased Tg and Nis expression, suggesting a TPY1-induced decreasein the TSH-stimulated TSH receptor activity. TPY1 also increasedthe gene expression of the TSH β-subunit and thyroliberin receptorgenes in the pituitary gland, which may be due to a higher thresholdof sensitivity of thyrotrophs to the inhibitory effect of T3 underconditions of long-term T3 hyperthyroidism. A distinctive featureof cold-induced T3 hyperthyroidism in rats was the tissue specificityof changes in DIO2 gene expression,namely its increase in the TG and a decrease in the hypothalamus,as well as the retention of elevated DIO2 geneexpression in the TG after TPY1 treatment. Thus, prolonged exposureof rats to cold leads to the development of pronounced T3 hyperthyroidismwith increased expression of genes responsible for TH synthesis,while the treatment with an allosteric TSH receptor antagonist significantlynormalizes these indices.