Androgen-regulated microRNAs as relevant effectors of adipogenesis inhibition

迟发性性腺功能减退症（洛）及其相关症状，例如代谢综合征发病率增加，2型糖尿病和心血管疾病将在未来几十年的公共卫生系统中发挥重要作用，考虑到西方社会人口老龄化的进展。由于血清雄激素水平降低而导致胰岛素敏感性降低，但这会影响洛缺失的负面后效。在这种情况下，雄激素、微小RNA如miR-375和其他雄激素调节的微小RNA与脂肪细胞分化所必需的几种分子因子如CEBPalpha、PPARgamma、瘦素和脂联素及其受体之间的相互作用将在前脂肪细胞模型（SGBS）中进行体外研究，并在功能和机制上进行描述。此外，对洛潜在的新型治疗药物（选择性雄激素受体调节剂- SARMs）的分析将在基础研究相关的体外研究和临床实践之间建立桥梁。

Late-onset hypogonadism (LOH) as well as its associated symptoms like an increased prevalence for the development of a metabolic syndrome, type 2 diabetes and cardiovascular diseases will play an important role in the public health system of the future decades considering the progressing demographic ageing of western societies.Aim of the analyses underlying this proposal is the evaluation of potential signaling pathways favoring adipocytic differentiation and a decreased insulin sensitivity due to lowered androgen serum levels and though that causally influencing the negative after-effects of LOH. In this context the interaction between androgens, microRNAs like miR-375 and further androgen-regulated microRNAs and several molecular factors essential for adipocytic differentiation like CEBPalpha, PPARgamma, leptin and adiponectin as well as their receptors will be studied in-vitro in a preadipocytic cell model (SGBS) and functionally and mechanistically described. Additionally, the analyses of potential novel therapeutics (selective androgen receptor modulators - SARMs) of LOH will build a bridge between basic research-related in-vitro studies and the clinical praxis.