睾酮调控肝脏miR-361-5p/miR-125a-5p在LOH中的作用及机制研究

Late-onset hypogonadism (LOH) in the aging male is a clinical and biochemical syndrome caused by an age-related decline in testosterone. Due to the wide effects of testosterone in body, LOH causes comorbidities in multiple organs and seriously decreases the quality of life. Current studies mainly focus on the characteristics, diagnosis and treatment of the disease. The lack of molecular mechanisms analysis to a large extent limits the progress in the diagnosis criteria and therapeutic measures of LOH. microRNAs (miRNAs) have been found to play important roles in many diseases. And testosterone can directly regulate the expression of miRNAs. So herein we speculate the decline of testosterone in LOH may induce the deregulation of miRNAs and in turn affects the gene expression and organ function, which might be one of the molecular mechanisms of LOH. Our previous studies have identified the dis-regulated miRNAs in LOH patients. On the basis of further experiment results, the present research task intends to analyze the mechanism in the impact of testosterone on miR-361-5p/miR-125a-5p and the subsequent effects on hepatocyte functions, which may contribute to the pathogenesis of LOH. This study may provide new prospects and targets in the diagnosis and treatment of LOH.

男性迟发性性腺功能减退症（LOH）是中老年男性睾丸功能逐渐衰退，睾酮逐渐降低而导致的临床和生化综合征。由于睾酮作用广泛，因此LOH对机体多个器官的衰老和功能有不利影响，严重影响生活质量。相关研究主要集中于对诊断和发生特征的研究，而分子机制研究缺乏，很大程度上限制了LOH诊断指标和治疗措施的研究进展。miRNA在诸多疾病的发生中起重要作用，而睾酮能直接调控miRNA的表达，我们推测LOH发生时，由于睾酮水平降低，导致miRNA表达失调，进而影响基因表达和器官功能，是LOH发生和器官衰老的分子机制之一。我们前期已鉴定出LOH患者失调的miRNAs，在进一步实验分析的基础上，本课题拟研究睾酮调控miR-361-5p/miR-125a-5p的机制，以及睾酮调控这两个miRNAs对肝细胞功能的影响和分子机制，分析这种机制在LOH发生中可能的作用，为LOH的诊断和治疗提供新分子和思路。