## 3 Discussion
In the diabetic and aging rats, as well as in young adult animals, the stimulating effect of TP4/2 on the blood T levels in the first two days of treatment was lower than for hCG, but, starting from the third day, it was similar to the hCG effect (Figure 3). The reason for this, we believe, is the maintaining of the _Lhr_ gene expression in diabetic rats treated with TP4/2. In the case of hCG treatment, the _Lhr_ gene expression was significantly decreased in both diabetic and aging rats, to the greatest extent in T1 DM (Figure 4). It should be noted that there are many early works on a decrease in the number and expression of LHCGR in target cells when they are treated with gonadotropins with LH activity [67; 68; 69]. A decrease in the expression of the _Lhr_ gene is due to the triggering of the mechanism of negative feedbacks, which are realized due to prolonged activation of LHCGR by gonadotropin [6]. This mechanism is due to the fact that, in contrast to effector-specific LMW allosteric agonists of LHCGR [16; 22], gonadotropins activate a wide range of signaling cascades [6; 7], and this can cause stimulation of intracellular pathways responsible for a decrease in the _Lhr_ gene expression. Moreover, in the diabetic and aging rats, under the conditions of increased inflammation and apoptosis in the testes, the negative effect of hCG treatment on the _Lhr_ expression was more pronounced than in the young adult animals. This, as can be assumed, is due to an impairment of some compensatory mechanisms that ensure the maintaining and restoration of the expression of LHCGR. Other authors showed a significant decrease in the efficiency of gonadotropin binding to LHCGR in the testes of rats with streptozotocin T1 DM [66; 70] and old animals [71], which is consistent with our results on the weakening of the _Lhr_ expression in the diabetic and aging testes (Figure 4). The fact that the steroidogenic effect of TP4/2 slowly but gradually increases when it is administered for five days may be due to its ability to penetrate the plasma membrane of the Leyd cells and bind to \"immutative\" forms of LHCGR localized intracellularly, such as was demonstrated for Org 43553 by other authors [37]. Thus, the TP derivatives can function as LMW chaperones for LHCGR. This may explain the fact that in T1 DM, when the post-translational processing of testicular proteins is impaired and a significant part of them are modified by glucose residues, TP4/2 retains the ability to activate LHCGR and is not inferior to hCG, despite the lower affinity for the receptor. In the young adult, aging and diabetic rats, the stimulating effect of TP4/2 on steroidogenesis was comparable to that of hCG, but an increase in the gene expression for steroidogenesis proteins was significantly less pronounced or was not detected (Figure 4). It was shown that TP4/2's stimulating effects on the _Star_ and _Cyp17a_ expression in the Young+TP group, the _Hsd3b_ and _Cyp17a_ expression in the Diab+TP group and the _Star_ expression in the Aging+TP group were lower compared to those of hCG in the same series of animals (Figure 4). Moreover, unlike hCG, five-day treatment with TP4/2 did not affect the _Cyp11a_ expression in the Young+TP, Diab+TP and Aging+TP groups and the _Hsd3b_ and _Cyp17a_ expression in the Aging+TP group (Figure 4). This indicates that stimulation of testicular steroidogenesis by LMW allosteric agonists does not require a significant increase in the expression of StAR and steroidogenic enzymes, which, as one can assume, is due to a more targeted activation of intracellular cascades in Leydig cells. Thus, under conditions of exposure to allosteric agonists of LHCGR, with a similar efficiency of stimulation of steroidogenesis with that of gonadotropins, a more moderate stimulation of the expression of genes of steroidogenesis occurs, without the overload of transcriptional mechanisms induced by hCG.