A decrease in the sensitivity of adenylyl cyclase and heterotrimeric g proteins to chorionic gonadotrophin and peptide hormones action in the tissues of reproductive system of rats with experimental type 2 diabetes

Patients with different forms of the diabetes, particularly with insulin-independent type 2 diabetes, have a wide spectrum of the disturbances of the functions of reproductive system. It is suggested that the main reason of these disturbances is altered sensitivity of reproductive system tissues to the regulatory action of hormones. The aim of this study was the identification of the changes in functioning of adenylyl cyclase system (ACS) sensitive to human chorionic gonadotrophin (hCG) and the peptide hormones in the ovary, testes and uterus of rats with neonatal streptozotocin (STZ) diabetes that is similar to the type 2 diabetes in humans. The effects of hCG, PACAP-38 and relaxin, realizing their effects via stimulatory G proteins (G_s), and somatostatin, acting via the inhibitory G protein (G_i), on adenylyl cyclase (AC) activity and GTP binding to the G proteins were studied. In rats with STZ type 2 diabetes the regulatory effects of hCG and PACAP-38 decreased in the ovary and testes, while the effects of somatostatin decreased in all investigated tissues (especially in the uterus). This caused attenuation of the hormonal effects, stimulating (hCG and PACAP-38) or inhibiting (somatostatin) AC activity, and in the decrease of their stimulatory effect on the GTP binding. At the same time a significant decrease of ACS sensitivity to relaxin in the tissues of diabetic rats was not found. Data obtained suggest that one of the key reasons for impairments of reproductive functions in experimental type 2 diabetes is the decrease of ACS sensitivity to the hormones, hCG, PACAP-38 and somatostatin, which play an important role in the reproductive system functioning.