## 2 Results
### The Effect of TP4/2 on the AC Activity in Thyroid Membranes and the Thyroid Hormones Levels  
Since the structure of the allosteric site of LHCGR is similar to that of thyroid stimulating hormone receptor (TSHR), we studied the effect of TP4/2 on the AC activity in the rat thyroidal membranes in in vitro conditions and on the baseline and thyrotropin-releasing hormone (TRH)-stimulated blood levels of thyroid hormones in young adult rats in in vivo conditions. In the in vivo experiments, TRH was administered intranasally (300 ug/kg), as previously described [42]. No significant effect of TP4/2 (10\({}^{-5}\) M) on the basal and forskolin-, GpNHp- and TSH-stimulated AC activity in the rat thyroidal membranes was found (Table S2). With a single administration to rats, TP4/2 at a dose of 20 mg/kg had no effect on the baseline and TRH-stimulated blood levels of free and total thyroxine and total triiodothyronine within 3.5 h after TP4/2 administration (Table S3). The Effect of Five-Day Treatment of the Young Adult, Aging and Diabetic Rats with TP4/2 and hCG on the Blood Testosterone Level and the Intruesticular Content of Testosterone and Its Precursors  
During five days of administration, in young adult rats, the stimulating effect of TP4/2 on blood T levels remained unchanged (Figure 3A). On the first and second days, the corresponding effect of hCG was maximal and, on average, 2.5 times higher than that of TP4/2. On the third, fourth and fifth days, this effect was decreased and did not differ from that of TP4/2 (\(p>0.05\)) (Figure 3A). The calculated AUC\({}_{0-5}\) values for TP4/2 and hCG stimulating effects were significantly higher than in untreated groups, and the AUC\({}_{0-5}\) for hCG effect was 58% higher than that for TP4/2 effect (Figure 3D). The ratio between stimulating effects of TP4/2 and hCG increased from 0.36 on the first day to 0.80 on the fifth day, which indicates a decrease in the differences in the effectiveness of these drugs in the case of five-day administration (Figure 3E). Five-day treatment with TP4/2 and hCG increased the intruesticular content of 17-hydroxyprogesterone, androstenedione and T in young adult animals (Table 2). The intruesticular 17-hydroxyprogesterone content in the group Young+hCG was significantly higher than that in the group Young+TP, while the content of T and other hormones in these groups did not differ significantly (Table 2). Figure 3: Cont. Figure 3: The effects of five-day treatment of the young adult, aging and diabetic male rats with TP4/2 and hCG on the blood testosterone levels. (**A**) Young+dmso—young adult rats plus DMSO, i.p. ; Young+TP—young adult rats plus TP4/2, 20 mg/kg, i.p. ; Young+saline—young adult rats plus saline, s.c.; Young+hCG—young adult rats plus hCG, 20 IU/rat, s.c.; (**B**) Aging+dmso—aging rats plus DMSO, i.p. ; Aging+TP—aging rats plus TP4/2, 20 mg/kg, i.p. ; Aging+saline—aging rats plus saline, s.c.; Aging+hCG—aging rats plus hCG, 20 IU/rat, s.c.; (**C**) Diab+dmso—diabetic rats plus DMSO, i.p. ; Diab+TP—diabetic rats plus TP4/2, 20 mg/kg, i.p. ; Diab+saline—diabetic rats plus saline, s.c.; Diab+hCG—diabetic rats plus hCG, 20 IU/rat, s.c.; (**D**) the AUC0-5 value for the “T concentration (nmol/L)–time (days)” curves calculated for each of the studied groups and were given in relative units; (**E**) the ratio between stimulating effects of TP4/2 and hCG (the T concentration increases caused by these drugs over the baseline T concentration at the day “0”). The drugs were administered every day at 10.00, and the blood T levels were measured 3 h after the treatment (at 13.00), when the steroidogenic effects reaches saturation.