Estrogens and Progestins

This chapter reviews the actions of estrogen and progesterone on bone. The effects of sex steroids on the skeleton are complex. Multiple receptor isoforms for the estrogen receptor (ER) and progesterone receptor (PR) have been identified in bone cells. Sex steroids influence sexual dimorphism and reproductive functions of the skeleton. In the process they modify bone growth and remodeling. Estrogens regulate osteoblast-mediated bone formation and osteoclast-mediated bone resorption at multiple levels, including progenitor cell recruitment, proliferation, differentiation, and programmed cell death. In contrast to estrogen, the role of progesterone in bone physiology is less well understood. This chapter deals with the skeleton as a reproductive organ and ER and PR structure and function. Following this, it considers the roles of the receptor isoforms and receptor coregulators. It also explains receptor isoform expressions in skeletal tissues, and alternative pathways of estrogen action, throwing light on the effects of treatment with estrogen and progesterone on bone cells in vitro and on the skeleton in vivo. Furthermore, it explains sex steroid metabolism, and consequences of ER and PR gene deletions on skeletal structure and bone metabolism. Finally, owing to the increasing clinical and scientific interest in these substances, it discusses the actions of estrogen-related compounds (selective estrogen receptor modulators or SERMs, estrogen metabolites, and phytoestrogens) on the skeleton.