## Materials and Methods
### Animals  
The male Wistar rats (_Rattus norvegicus_) were obtained from the \"Rappolovo\" animal nursery (Leningrad Region, Russia). The animals were housed in the plastic cages, five animals in each, with a 12 h light/12 h dark cycle and temperature (23 \(\pm\) 3 \({}^{\circ}\)C) and had free access to laboratory chow pellets and water. The daily standard diet in all the studied groups contained 20-25 g of dry food (19% protein, 5% fat, 4% fiber, and 9% ash), which provided 2.95 kcal/g. Three-month-old rats were used for T1 DM induction, and 18-month-old rats were considered as aging animals. The experimental procedures were approved by the Institutional Animal Care and Use Committee at the Sechenov Institute of Evolutionary Physiology and Biochemistry (St. Petersburg, Russia) (Protocol No. 01/2019, 29 January 2019) and according to \"The Guide for the Care and Use of Laboratory Animals\" and the European Communities Council Directive recommendations for the care and use of laboratory animals (2010/63/EU). All efforts to minimize animal suffering and to reduce the number of animals were made.  
The Selection of the Doses and Delivery Routes for TP4/2 and hCG and the Estimation of Thyroid Hormone Levels in TP4/2-Treated Rats  
The choice of the doses for TP4/2 and hCG and the method of drug delivery was carried out on the basis of preliminary studies with Young adult (four-month-old) male Wistar rats.  
To determine the optimal dose for different routes of drug administration, the TP4/2 and hCG were administered intraperitoneally and subcutaneously at the doses from 5 to 50 mg/kg for TP4/2 and from 5 to 100 IU/rat for hCG. At each dose, the volume of the TP4/2 solution was 200 \(\mu\)L (in DMSO), and the volume of the hCG solution was 200 \(\mu\)L (in saline). Control animals received either DMSO (in the experiments with TP4/2) or saline (in the experiments with hCG) in the same volume and with the same route of administration. The drugs or their solvents were administered at 10.00. In these experiments, the steroidogenic effect of hCG and TP4/2 was assessed by the blood T level during 5 h after drugs administration (10.00-15.00) (Table S4).  
In the case of i.p. administration TP4/2, the maximal stimulating effect on the T production was observed at the doses 25 mg/kg and above, while in the case of s.c. administration hCG, the effect was observed at the doses 50 IU/rat and above. In accordance with this, the doses were selected in which the steroidogenic effect of TP4/2 and hCG was 70-80% of its maximum value, and these doses were 20 mg/kg for TP4/2 and 20 IU/rat for hCG in both routes of administration.  
At the same time, in the case of s.c. administration, the maximum stimulating effect of TP4/2 was less pronounced and had significant variability compared to i.p. administration, which, we believe, is due to the lower bioavailability of TP4/2 when administered subcutaneously. In the case of i.p. administration of hCG, the maximum steroidogenic effect of gonadotropin was lower than in the case of its s.c. administration, and had a significant variability. Based on these data, to study the steroidogenic effects of these drugs, we used i.p. administration of TP4/2 at a dose of 20 mg/kg and s.c. administration of hCG at a dose of 20 IU/rat.