Abstract

Previous studies evaluating the role of the androgen receptor (AR) for bone mass have used mouse models with global or tissue-specific lifelong inactivation of the AR. However, these mouse models have the AR inactivated already early in life and the relative roles of the AR during development, sexual maturation and in adult mice cannot be evaluated separately. The aim of the present study was to determine the specific roles of the AR in bone during sexual maturation and in adult mice. The AR was conditionally ablated at four (pre-pubertal) or ten (post-pubertal) weeks of age in male mice using tamoxifen-inducible Cre-mediated recombination. Both the pre-pubertal and the post-pubertal AR inactivation were efficient demonstrated by substantially lower AR mRNA levels in seminal vesicle, bone and white adipose tissue as well as markedly reduced weights of reproductive tissues when comparing inducible ARKO mice and control mice at 14 weeks of age. Total body BMD, as analyzed by DXA, as well as tibia diaphyseal cortical bone thickness and proximal metaphyseal trabecular bone volume fraction, as analyzed by μCT, were significantly reduced by both pre-pubertal and post-pubertal AR inactivation. These bone effects were associated with an increased bone turnover, indicating a high bone turnover osteoporosis. Pre-pubertal but not post-pubertal AR inactivation resulted in substantially increased fat mass. In conclusion, the AR is required for maintenance of both trabecular and cortical bone in adult male mice while AR expression during puberty is crucial for normal fat mass homeostasis in adult male mice.