Targeted Overexpression of Androgen Receptor in Osteoblasts: Unexpected Complex Bone Phenotype in Growing Animals

The androgen receptor (AR), as a classic steroid receptor, generally mediates biologic responses to androgens. In bone tissue, both AR and the estrogen receptor (ER) are expressed in a variety of cell types. Because androgens can be converted into estrogen via aromatase activity, the specific role of the AR in maintenance of skeletal homoeostasis remains controversial. The goal of this study was to use skeletally targeted overexpression of AR as a means of elucidating the specific role(s) for AR transactivation in bone homeostasis. Rat AR cDNA was cloned downstream of a 3.6-kb α1(I)-collagen promoter fragment and used to create AR-transgenic mice. AR-transgenic males gain less weight and body and femur length is shorter than wild-type controls, whereas females are not different. AR-transgenic males also demonstrate thickened calvaria and increased periosteal but reduced endosteal labeling by fluorescent labeling and reduced osteocalcin levels. High-resolution micro-computed tomography shows normal mineral...