Взаимосвязь между андрогенным дефицитом и ослаблением чувствительности аденилатциклазы к гонадотропинам в семенниках крыс со стрептозотоциновым диабетом различной степени тяжести

Abstract

Type 1 diabetes mellitus (DM1) leads to dysfunctions of the male reproductive system, which is caused by a decrease in testosterone (T) synthesis by the testes. Currently, there is little studied how the severity of DM1 affects the T production, and what role in the development of androgen deficiency is played by a decrease in the sensitivity of the adenylyl cyclase system of Leydig cells to gonadotropins. The aim of the work was to study the basal and human chorionic gonadotropin(hCG)-stimulated T levels in male rats with severe, moderate and mild forms of DM1, as well as to study the regulation of the enzyme adenylyl cyclase (AC) by non-hormonal agents (forskolin, GppNHp) and hCG in the testicular membranes of diabetic rats. The severe (D-T) and moderate (D-S) forms of DM1 were caused by treatment of four-month-old rats with streptozotocin at the doses of 60 and 35 mg/kg, and the mild form (D-M) was induced by treatment of five-day-old rat pups with streptozotocin (75 mg/kg), which led to the development of diabetes at the age of 4 months. The values ​​of AUC(11.00-18.00) (the integrated area under the curve “concentration of T(nM) –time(h)”) in the D-T, D-S and D-M groups was 50.4±10.4, 75.7±21.2 and 105.9±9.3 arb.u. and were reduced by 69, 53 and 34% in comparison with control (161.1±18.6 arb.u., p<0.05). The AUC(11.00-16.00) for the T level stimulated by hCG (100 IU/rat) in the same groups were 115.4±30.4, 229.6±64.3 and 306.4±58.8 arb.u. and were reduced by 74, 48 and 31% in comparison with control (445.4±132.7 arb.u., p<0.05). In the testicular membranes of rats of the D-T group, the basal and the forskolin-, GppNHp- and hCG-stimulated AC activity were decreased by 34, 39, 54 and 68%, respectively. In the D-S and D-M groups, only the AC effects of GppNHp and hCG were decreased. Thus, the androgen deficiency in rats with DM1 and the steroidogenic response in the case of their treatment with hCG depend on the severity of DM1, and the key cause of the androgen deficiency is the impaired functional activity of the gonadotropin-sensitive adenylyl cyclase system in the testes of diabetic rats.