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

Abstract

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 supposed that the main reason of these disturbances is altered sensitivity of reproductive system tissues to regulatory action of hormones. The aim of the work was the identification of the changes in functioning of human chorionic gonadotropin (hCG)--and peptide hormones-sensitive adenylyl cyclase system (ACS) 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 G-protein of the stimulatory type (Gs), and somatostatin, acting via G-protein of the inhibitory type (Gi), on adenylyl cyclase (AC) activity and the GTP binding of the G-proteins were studied. Regulatory effects of hCG and PACAP-38 decreased in the ovary and testes of rats with STZ type 2 diabetes, while the effects of somatostatin decreased in all investigated tissues (in a considerable extent in the uterus). This expressed in the weakening of hormonal effects on AC activity, stimulating in the case of hCG and PACAP-38 and inhibiting in the case of somatostatin, and in the decrease of stimulation of the GTP binding by the hormones. 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 the key reason of the disturbances of reproductive functions in experimental type 2 diabetes is the decrease of ACS sensitivity to the hormones, such as hCG, PACAP-38 and somatostatin, that play a important role in functioning of reproductive system.