Shpakov A O, Derkach K V, Bondareva V M
Biomed Khim. 2010 Nov-Dec;56(6):700-9. doi: 10.18097/pbmc20105606700.
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.
患有不同类型糖尿病的患者,尤其是非胰岛素依赖型2型糖尿病患者,存在广泛的生殖系统功能紊乱。据推测,这些紊乱的主要原因是生殖系统组织对激素调节作用的敏感性改变。本研究的目的是确定在新生链脲佐菌素(STZ)诱导的糖尿病大鼠的卵巢、睾丸和子宫中,人绒毛膜促性腺激素(hCG)和肽类激素敏感的腺苷酸环化酶系统(ACS)的功能变化,该糖尿病模型类似于人类的2型糖尿病。研究了hCG、垂体腺苷酸环化酶激活肽-38(PACAP-38)和松弛素通过刺激性G蛋白(Gs)发挥作用,以及生长抑素通过抑制性G蛋白(Gi)发挥作用,对腺苷酸环化酶(AC)活性和G蛋白的GTP结合的影响。在STZ诱导的2型糖尿病大鼠的卵巢和睾丸中,hCG和PACAP-38的调节作用降低,而生长抑素在所有研究组织中的作用均降低(在子宫中降低程度较大)。这表现为激素对AC活性的影响减弱,hCG和PACAP-38起刺激作用,生长抑素起抑制作用,以及激素对GTP结合的刺激作用降低。同时,未发现糖尿病大鼠组织中ACS对松弛素的敏感性显著降低。所得数据表明,实验性2型糖尿病生殖功能紊乱的关键原因是ACS对hCG、PACAP-38和生长抑素等在生殖系统功能中起重要作用的激素的敏感性降低。