[Preservation of the stimulatory effect of thyroid stimulating hormone receptor allosteric agonist on thyroid hormone level in aging rats with obesity].

In conditions of aging, the functions of the thyroid gland (TG) change, and in obesity these changes are expressed to a greater extent and often lead to the resistance of the TG to the thyroid-stimulating hormone (TSH) and a deficiency of thyroid hormones (TH). One of the approaches to compensate for the TH deficiency may be the use of allosteric agonists of the TSH receptor, including the compound TPY3m developed by us. The aim of the work was to study its effect on the thyroid status in aging (18 months) male Wistar rats with and without obesity in comparison with thyroliberin (TRH), which increases the level of TSH in the blood. Obesity was induced by a 12-week high-fat diet (from the age of 15 months), TPY3m was administered at a dose of 20 mg/kg (i.p.), and TRH at a dose of 100 μg/rat (intranasally). The levels of free thyroxine (fT4), free and total triiodothyronine (fT3, tT3) and TSH were determined using ELISA. In aging rats without obesity (С18), no significant changes in thyroid status were found compared to young rats (5 months, С5), with the exception of a decrease in the fT3 level. In aging obese animals (OB18), compared to С18, the levels of fT4 and fT3 were decreased, the level of TSH was increased (by 76%), and the integrated thyroid index (ITI) was decreased (by 58%), which indicates a weakening of TH synthesis and the development of thyroid resistance to TSH. TRH increased the levels of TH and TSH in all groups. However, the TRH-induced increase in the fT4 level in the C18+TRH group was lower than in C5+TRH, and in the OB18+TRH group it was lower than in C18+TRH. In the OB18+TRH group, a tendency towards a decrease in the TRH-induced increase in fT3 was also shown. At the same time, the stimulating effect of TPY3m on TH levels in all studied groups of animals was characterized by stability and did not depend on diet and age. This indicates that the magnitude of the stimulatory effects of TPY3m on TH levels and TSH receptor sensitivity in rats is maintained with age and obesity, suggesting that TPY3m may be useful for developing drugs to compensate for TH deficiency in aging and metabolic disorders.