Androgen-regulated microRNAs as relevant effectors of adipogenesis inhibition

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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.