Androgen Action in Bone: Basic Cellular and Molecular Aspects

Abstract

The impact of the menopause on skeletal health is obvious, but there remains confusion interpreting the skeletal actions of sex steroids. Thus, the mechanisms by which androgens affect bone homeostasis are becoming the focus of intensified research. As a classic steroid hormone, the biological cellular signaling responses to androgen are mediated through the androgen receptor (AR), a ligand-inducible transcription factor. Androgen effects on bone may also be indirectly modulated and/or mediated by other autocrine and paracrine factors in the bone microenvironment or through steroid metabolic enzymatic activity. ARs have been identified in a variety of cells found in bone, thus clearly identifying bone as a target tissue for androgen action. The direct effects of androgen that influence the complex processes of proliferation, differentiation, mineralization, and gene expression in the osteoblast are being characterized, but much remains controversial. This chapter will review recent progress on characterization of the molecular and cellular mechanisms that underlie androgen action in bone.