Institute of Experimental Physiology, National Scientific and Technical Research Council (IFISE-CONICET), Suipacha 531, PC 2000, Rosario, Argentina.
Pharmacology, Faculty of Biochemical and Pharmaceutical Sciences, National University of Rosario, Suipacha 531, PC 2000, Rosario, Argentina.
Mol Cell Endocrinol. 2021 Mar 15;524:111170. doi: 10.1016/j.mce.2021.111170. Epub 2021 Jan 19.
Accumulating evidence indicates the association between changes in circulating sex steroid hormone levels and the development of diabetic nephropathy. However, the renal synthesis of steroid hormones during diabetes is essentially unknown. Male Wistar rats were injected with streptozotocin (STZ) or vehicle. After one week, no changes in functional or structural parameters related to kidney damage were observed in STZ group; however, a higher renal expression of proinflammatory cytokines and HSP70 was found. Expression of Steroidogenic Acute Regulatory protein (StAR) and P450scc (CYP11A1) was decreased in STZ kidneys. Incubation of isolated mitochondria with 22R-hydroxycholesterol revealed a marked inhibition in CYP11A1 function at the medullary level in STZ group. The inhibition of these first steps of renal steroidogenesis in early STZ-induced diabetes led to a decreased local synthesis of pregnenolone and progesterone. These findings stimulate investigation of the probable role of nephrosteroids in kidney damage associated with diabetes.
越来越多的证据表明，循环性激素水平的变化与糖尿病肾病的发生发展有关。然而，糖尿病期间类固醇激素在肾脏中的合成基本上是未知的。雄性 Wistar 大鼠被注射链脲佐菌素（STZ）或载体。一周后，STZ 组的肾功能和结构参数无明显变化；然而，发现促炎细胞因子和 HSP70 的肾表达更高。STZ 肾脏中的 Steroidogenic Acute Regulatory protein (StAR) 和 P450scc (CYP11A1) 的表达减少。用 22R-羟胆固醇孵育分离的线粒体表明，在 STZ 组中，皮质醇的 CYP11A1 功能在髓质水平受到明显抑制。早期 STZ 诱导的糖尿病中这些肾甾体生成的第一步的抑制导致孕烯醇酮和孕酮的局部合成减少。这些发现促使人们研究肾甾体在与糖尿病相关的肾脏损伤中的可能作用。
