Androgens Receptor Expression and Steroid Action in Bone

Adrogens, in both men and women, have important beneficial effects on skeletal development and on the maintenance of bone mass. Studies have demonstrated that androgens influence growth plate maturation and closure (thus helping to determine longitudinal bone growth during development) mediate regulation of cortical bone mass in a fashion distinct from estrogen (leading to a sexually dimorphic skeleton, modulate peak bone mass acquisition), and influence trabecular (cancellous) bone and inhibit bone loss. Androgens are important in the maintenance of a healthy skeleton, and have been shown to stimulate bone formation in the periosteum but reduce formation on the endosteal surface in cortical bone and in trabecular bone and reduce osteoclast activity. Androgens influence skeletal modeling and remolding by multiple mechanisms through effects on osteoblasts, osteoclasts, and even perhaps an influence on the differentiation of pluripotent stem cells toward distinct lineages. The specific effects of androgen on bone cells are mediated directly through an androgen receptor-signaling pathway, but there are also indirect contributions to overall skeletal health through aromatization and estrogen receptor signaling. The interaction of androgens and estrogens, and their respective actions in the skeleton and in other tissues can be utilized for specific diagnostic and therapeutic benefit.