The Androgen Biology Group in the Laboratory of Reproductive and Developmental Toxicology was established in 2003. We are studying the pharmacology of tissue-selective androgen receptor modulators. The methods employed involve capitalizing upon unique non-steroidal androgen agonists and antagonists that are naturally fluorescent. We use both cell- and animal based assays to investigate the pharmacodynamics of these compounds, with particular reference to their utility to determine the mechanism of tissue selectivity. The principal compound of interest fluoresces in the visible, and also elicits singlet-oxygen species with high quantum yield. Irradiation of live cells in culture on the microscope stage generates a cell-killing effect that is time- light- and compound concentration dependent. Cells progress through a permeable stage visualized via propidium iodide staining, followed subsequently by a cytolytic phase resulting in cell death. We are investigating the mechanism of this pathway. A second research activity involves studies of the role of androgen receptor modulators as controllers of stem cell differentiation in vitro. Published evidence for androgen effects to shift stem cells towards a myoid pathway as opposed to an adipocytic pathway supports a role for endocrine disruptors as environmental factors affecting obesity in humans. The mechanism and sensitivity of this process to androgen agonists and antagonists is currently the focus of this aspect of our work.
