Obesity is often accompanied by hypothyroidism, the severity of which worsens with aging, which may be due to a decrease in the sensitivity of thyrocytes to thyroid-stimulating hormone (TSH). Thyroid hormone replacement therapy is usually used to compensate for thyroid hormone (TH) deficiency, but it has significant limitations. Allosteric TSH receptor agonists, including our developed TPY3m, a thieno[2,3-d]-pyrimidine derivative, may be proposed as an alternative. The aim of this study was to compare the effects of TPY3m and thyroliberin (TRH) on TH and TSH levels in the blood of aging rats, including obese ones. Male rats (18-month-old) were administered TPY3m (20 mg/kg, i.p.) and TRH (100 μg/rat, intranasally). Obesity was induced by a 12-week high-fat diet (OB). Hormone levels (fT4, fT3, tT3, TSH) were assessed using ELISA, calculating the index of peripheral conversion ([fT3]/[fT4], IPC) and the integral thyroid index ([fT3]+[fT4]/[TSH], ITI). In aging obese rats, the fT3 level, ICI and ITI were reduced. Treatment of the OB group with TRH increased TSH and fT4 levels, but to a lesser extent than in the control. The ITI index remained reduced. TPY3m increased fT4 and fT3 levels in the OB and control groups, but, unlike TRH, did not affect the TSH level, increased the ITI, and normalized the ICI. Thus, TPY3m similarly stimulated TH production in aging rats with and without obesity, whereas the stimulatory effects of TRH were reduced in obesity, indicating that the sensitivity of the TSH receptor to allosteric agonists is preserved in aging and obesity.
The study was supported by the RSF (No 19-75-20122).