Changes in Hormone Sensitivity of the Adenylate Cyclase Signaling System in the Testicular Tissue of Rats with Neonatal Streptozotocin-Induced Diabetes

Abstract

Activity of the adenylate cyclase signaling system was evaluated in the testicular tissue of rats with neonatal streptozotocin-induced diabetes (120 and 180 days duration). This state is similar to type 2 diabetes in humans. The regulation of this system by polypeptide hormones and biogenic amines was studied. Sensitivity of the adenylate cyclase signaling system to the regulatory effect of human chorionic gonadotropin and PACAP (pituitary adenylyl cyclase-activating polypeptide) was significantly reduced. The effects of these agents are realized via stimulatory G proteins. Somatostatin, acting through inhibitory G proteins, produced less pronounced effect on the adenylate cyclase signaling system. The increase in the duration of diabetes was accompanied by a decrease in the stimulatory effects of human chorionic gonadotropin and PACAP on adenylate cyclase. Sensitivity of the adenylate cyclase signaling system to biogenic amines remained unchanged (serotonin) or increased under these conditions (epinephrine). Our results indicate that changes in hormonal regulation of the adenylate cyclase signaling system and functional activity of cAMP-dependent signaling cascades are important factors for dysfunction of spermatogenesis and steroidogenesis during insulin-independent diabetes.

The stimulating influence of thienopyrimidine compounds on the adenylyl cyclase signaling systems in the rat testes

“…In the testicular membranes, hCG (10 -8 M) increased the basal AC activity by 558% and GTP binding by 122%, which corresponds to the previously found stimulatory effects of gonadotropin on the ACSS activity in rat testes [13,14]. In the membranes preincubated with compounds 1 and 2, the stimula tory effects of hCG on the AC activity and GTP bind ing were retained (Fig.…”

The functional activity of adenylyl cyclase signaling system in the brain, myocardium, and testes of rats with 8- and 18-month neonatal diabetes

“…2). As was shown by us and other authors earlier, the attenuation of G i coupled signaling pathways in DM is based on a decrease in the functional activity of G i proteins [5,8,11]. However, in older diabetic rats, increased expression of G i pro teins in the myocardium was observed, which probably explains the fact that the inhibitory effect of soma tostatin on AC in them was retained.…”

“…To monitor the patholog ical changes in the nervous, cardiovascular, and repro ductive systems in type 2 diabetes, we studied the func tional state of adenylyl cyclase signaling system (ACSS) in the brain, myocardium, and testes of dia betic animals. We have previously shown that distur bances in the ACSS are one of the main causes of development of diabetes complications, and the sever ity of these disorders is positively correlated with the severity and duration of the disease [4][5][6][7][8]. The basal activity of adenylyl cyclase (AC) and its regulation by hormones in the tissues of rats with 18 month long neonatal DM was compared with those in age matched healthy animals (control) as well as with 8 month old diabetic and control rats.…”