The androgen testosterone is a master regulator of physiology with well-established roles in metabolism, sex, and cancer. It is known that hormones in circulation decline with age and androgen replacement treatments may have health benefits for ageing men and women by maintaining muscle and bone strength and cardiovascular health. However, this is hotly debated, and more research is required regarding the safety and effectiveness of testosterone-based treatments.
Testosterone works inside cells by binding to a protein called the androgen receptor, which then seeks and binds to specific sequences located in the genetic material (DNA), where it can act to switch on or off specific genes. The details of how the hormone-receptor complex does this are poorly understood. Our aim is to build mathematical models that will simulate the function of the receptor, by integrating key steps in this pathway, and allow predications on gene expression (output) with respect to changes in hormones levels (input). To build these mathematical models we need to fill gaps in the biological information.
This pilot study will generate information on how changes in hormone switch on the androgen receptor and allow binding to different sites in the DNA and changes in gene expression. For the first time, this will allow us to link changes in hormone levels with gene selection and expression.