Estrogen Signaling in Bone.

Estrogen plays important roles in bone homeostasis throughout a person's life, including longitudinal bone growth, bone healing, and adaptation to mechanical forces. Estrogen exerts its action by binding to its multiple receptors in the cell membrane and cytoplasm. Until now at least three estrogen receptors (ER) have been reported: ER alpha (ERα), ER beta (ERβ), and G-protein coupled estrogen receptor 1 (GPER1) also known as GP30. Recently it has been observed that estrogen crosstalk with other signaling pathways helping to understand its wide effects in bone homeostasis. Abrupt loss of estrogen production experienced by menopausal women is associated with the rapid loss of bone mass ultimately leading to osteoporosis. The detrimental results during its absence with aging and the increased life expectancy of current and future generations make it of high importance to fully understand its mechanism of action. This review article aims to update on (1) the molecular mechanism of action of estrogen in the skeletal system, (2) ERs expression in different bone cells, (3) recent reported ER mutations resulting in pathological human conditions, and (4) role of estrogen signaling during bone healing.