Fig. 3.

Indirect actions of estrogen control bone remodeling. Estrogen production by the ovaries is stimulated by FSH secreted by the pituitary gland. Estrogens inhibit FSH secretion through negative feedback regulation mediated by the pituitary ER. Estrogen deficiency increases FSH secretion and stimulates production by bone marrow and immune cells of cytokines, such as TNFα and several ILs. These cytokines facilitate osteoclast differentiation from hematopoietic stem cells. As an opposing action, ovarian estrogens and GH from the pituitary gland induce hepatic production of IGF-I that stimulates osteoblast differentiation.