Chapter 37 – Estrogens and Progestins

Publisher Summary This chapter focuses on the structure and function of estrogens and progestins. The physiological actions of sex steroids contribute to sexual dimorphism of the skeleton, timing of epiphyseal closure, determination of peak bone mass, maintenance of mineral homeostasis during reproduction, and maintenance of bone mass, architecture, and mineral homeostasis in adults. Estrogen (E) is the major sex steroid that affects the growth, remodeling, and homeostasis of the skeleton. E regulates the processes of osteoblast (OB)-mediated bone formation and osteoclast (OC)-mediated bone resorption at multiple levels, which includes progenitor cell recruitment, proliferation, differentiation, and programmed cell death. Additionally, a second estrogen receptor distinct from the classical receptor has been identified, and loss-of-function mutations for these two receptor isoforms produce different skeletal phenotypes in mice. The activity of steroid nuclear receptors is modulated by the family of steroid receptor coregulators, which is composed of coactivators and corepressors. Coactivators, when bound to active receptor conformations, mediate favorable interactions with the basal transcriptional machinery, stabilize the preinitiation complex and, overall, stimulate gene transcription. Conversely, corepressors bind preferentially to inactive receptor conformations and prevent the interaction of the receptor with coactivators, thus resulting in nonproductive transcription factor complexes, which suppress gene transcription. Progesterone (P) is often given in conjunction with E during hormone replacement therapy of postmenopausal women to minimize some of the undesirable effects of E on reproductive tissues. P has been shown to stimulate mineralization of newly induced bone in rats and to increase the cortical bone formation rate in spayed Beagle dams.