The kidney as a non-classical target organ for androgen action

Androgens with testosterone as most important androgen are male sex hormones (sex steroids) that bind to the androgen receptor (AR). The structure of the receptor is known, but the role of androgen action in many organs has not been fully elucidated. It is known that androgens are important in many biological processes, including the development and maintenance of the bone. When androgens are low, the risk for bone loss (osteoporosis) increases. Mice have been generated without AR (knockout), leading to dramatic bone loss. However, when the AR is only absent in bone cells, much less bone loss is seen, suggesting that androgens have effects on ‘non-classical’ organs, by this way (indirectly) influencing the bone. This research project focuses on the kidney as a non-classical target organ for androgens. The kidneys are a key player in the regulation of the body's calcium and phosphate balance, and calcium and phosphate are essential for normal bone. The kidney is also the main organ for the production of active vitamin D, a hormone that is crucial for normal calcium and phosphate balance in the body. Moreover, we and others have shown that the AR is highly expressed in the human and mouse kidney. Our first aim is to study if very low androgen levels (after castration of male mice) lead to changes in calcium and phosphate handling by the kidney. Our second aim is the generation of a mouse model without AR in the kidney, and study if this mouse has abnormal bone and kidneys.