Institute of Radiobiology, Belarus National Academy of Sciences, Gomel, Belarus.
Int J Radiat Biol. 2010 Mar;86(3):238-51. doi: 10.3109/09553000903422548.
The aims of this work were: (i) To compare the effects of ionising radiation (IR) on testosterone binding globulin (TeBG) characteristics (serum concentration, cooperativity of androgen binding and affinity for hormone) in divergent mammalian species; (ii) to couple radiation effects with probable TeBG-parameter changes; and (iii) to investigate the prevention of these changes by fungal preparations (in particular - by lipid polyene complexes of Laetiporus sulphureus).
Characteristics of TeBG were investigated in microaliquots of rat and human serum samples using [(3)H]-5 alpha-dihydrotestosterone ([(3)H]-DHT) radioligand assays after in vivo exposures to IR (external gamma-sources, incorporation of (131)I-, (137)Cs-radionuclides) at experimental and post-Chernobyl radioecological conditions (doses 0.25-2.2 Gy).
Species-specific changes of TeBG parameters were found depending on the type of IR, dose and time after irradiation. Specifically children living in radionuclide contaminated regions (near Chernobyl) were found to have a decrease of positive cooperativity for the TeBG-androgen binding, a drop of TeBG levels, and a decline in hormone affinity. Screening of natural substances (from phanerogams and fungi) detected that lipid polyene complexes of the basidiomycete L. sulphureus allowed recovery of the standard features of TeBG.
IR induced a depletion of TeBG from blood simultaneously with species-specific changes of TeBG, which depend on the type of radiation, the dose of radiation (from 0.25 up to 2.2 Gy), and the time after radiation. The Hill coefficient of TeBG (indicating the degree of molecular cooperativity when hormone binding) appeared to be the most radiosensitive marker of the glycoprotein activity because of it is inversely to radiation dose. There are pharmacological possibilities to restore IR-induced "declines" of TeBG's affinity and cooperativity for androgen ligand binding.
本研究的目的在于:(i)比较不同哺乳动物物种中电离辐射(IR)对睾酮结合球蛋白(TeBG)特性(血清浓度、雄激素结合的协同性和激素亲和力)的影响;(ii)将辐射效应与可能的 TeBG 参数变化相关联;(iii)研究真菌制剂(特别是硫磺多孔菌的脂多烯复合物)对这些变化的预防作用。
使用放射性配体[(3)H]-5α-二氢睾酮([(3)H]-DHT),对大鼠和人血清样本中的微量 TeBG 特征进行了研究。这些血清样本来自于在实验和切尔诺贝利后放射性生态学条件下(剂量 0.25-2.2 Gy)进行的体内暴露(外γ源,(131)I-、(137)Cs 放射性核素的掺入)。
发现了 TeBG 参数的物种特异性变化,具体取决于 IR 的类型、剂量和照射后时间。具体而言,生活在放射性核素污染地区(切尔诺贝利附近)的儿童发现,TeBG-雄激素结合的正协同性降低,TeBG 水平下降,激素亲和力降低。对天然物质(来自于显花植物和真菌)的筛选发现,担子菌硫磺多孔菌的脂多烯复合物可以恢复 TeBG 的标准特征。
IR 导致 TeBG 从血液中耗竭,同时伴随着 TeBG 的物种特异性变化,这些变化取决于辐射的类型、辐射剂量(从 0.25 到 2.2 Gy)和辐射后时间。TeBG 的 Hill 系数(指示激素结合时分子协同性的程度)似乎是糖蛋白活性的最敏感标记物,因为它与辐射剂量成反比。有药理学的可能性来恢复 IR 诱导的 TeBG 对雄激素配体结合的亲和力和协同性的“下降”。