Rationale for the research area
An increasing number of chemicals have been suspected of mimicking hormonal effects and altering steroid hormone regulation. Impaired regulation of steroid action contributes to major diseases, including sexual dysfunctions, hypertension, diabetes, osteoporosis, immune disorders, cardiovascular disease and cancer. Thus, there is a great demand for suitable tools to detect chemical-induced disturbances of steroid homeostasis as early as possible and to identify the chemicals responsible for the observed changes. Furthermore, tools are needed to characterize the mode of action of a given chemical that causes disturbances in steroid regulation.
The proposed project aims at 1) the development of multiplex-methods for quantification of steroids (steroid hormone profiling, steroidomics) in order to detect disturbances of steroid homeostasis, 2) the identification of suitable markers for altered function of specific enzymes/receptors, 3) the development of cell-based assays to elucidate mechanisms of action of chemicals disturbing steroid homeostasis, and 4) the development of in silico and in vitro tools for the identification of chemicals interfering with steroid homeostasis.
Regulatory authorities are participating in large-scale projects on chemical safety, focusing on substances that disrupt endocrine functions; however, the currently available methods and potential targets under investigation are still highly limited, and additional testing strategies are required. The tools to be developed in this project should help in the identification of potentially hazardous chemicals, and the steroidomic profiling should facilitate the investigation of modes of action in animals and thus risk assessment in humans.