350 rub
Journal Technologies of Living Systems №8 for 2009 г.
Article in number:
THE STUDY OF HORMONE-REGULATED ADENYLYL CYCLASE SYSTEM IN REPRODUCTIVE TISSUES OF RATS WITH EXPERIMENTAL DIABETES MELLITUS
Keywords: adenylyl cyclase heterotrimeric G-protein diabetes mellitus testis chorionic gonadotropin ovary
Authors:
A.O. Shpakov, V.M. Bondareva, K.V. Derkach, M.N. Pertseva
Abstract:
Diabetes mellitus (DM) is associated with impairments of reproductive system function in both male and female individuals. We supposed that the disturbances of hormonal signal transduction via adenylyl cyclase signaling system (ACSS) in reproductive tissues is a one of the main cause of pathophysiological changes in these tissues and lead to a wide spectrum of dysfunctions and complications in the reproductive system in the case of DM. To test that hypothesis, we focused on the study of functional activity of ACSS and its sensitivity to hormonal stimuli in the testis and the ovary of the rats with experimental type 1 and 2 DM (EDM1 and EDM2) induced by streptozotocin treatment. For study we chosen the following hormones, regulators of the reproductive system: 1) human chorionic gonadotropin (HCG), PACAP-38 and relaxin that realized their action on adenylyl cyclase (AC) via G protein of the stimulatory type (Gs), 2) somatostatin acting on AC via G protein of the inhibitory type (Gi), and 3) biogenic amine serotonin acting on the enzyme via both Gs and Gi proteins. Basal AC activity and GTP binding in the testis and ovary of diabetic rats were decreased. This data speaks in favor of the fact that the functions of heterotrimeric G proteins and AC in re-productive tissues of the rats with EDM are reduced. HCG, PACAP-38 and, to a lesser extent, re-laxin stimulated the AC activity and GTP binding in the testis and the ovary of control rats. In the condition of EDM1 and EDM2 the stimulating effects of HCG were significantly decreased in the both tissues, the corresponding effects of PACAP-38 were reduced in the testis and, to a lesser ex-tent, in the ovary, while the stimulating effects of relaxin were preserved. Somatostatin inhibited both forskolin- and HCG-stimulated AC activities and stimulated GTP binding in the both tissues of control rats. The regulatory effects of somatostatin on ACSS strongly decreased in the condition of EDM, especially EDM2. The stimulating effects of serotonin on basal AC activity in diabetic and control tissues were similar. At the same time, the stimulating effects of the hormone on GTP binding and its inhibitory effects on forskolin-stimulated AC activity were reduced in the testis and the ovary of diabetic animals. Using peptide strategy we showed that in the condition of EDM are preferably disturbed the transduction of serotonin signal via ACSS coupled with Gi proteins. This gave grounds to suggest the weakening of inhibitory influence of somatostatin and serotonin on AC activity in reproductive tissues of the rats with EDM. Our results suggest that alterations in carbohydrate homeostasis in the condition of the EDM lead to a decrease of sensitivity of reproductive tissues to the action of the hormones, regulators of ACSS, especially acting via Gi proteins, and provokes the disturbances of functional activity of the reproductive system of laboratory animals with EDM.
Pages: 11-20
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