Receptor–activated G proteins are bound to the inside surface of the cell membrane. They consist of the Gα and the tightly associated Gβγ subunits. At the present time, three main families exist for Gα subunits: Gαs, Gαi, Gαq. These groups differ primarily in effector recognition, but share a similar mechanism of activation. G protein coupling enables membrane ERs to initiate signal transduction at the cell surface in different cell types. In female rat osteoblasts estrogen induced a rapid increase in intracellular calcium concentration and the formation of inositol 1,4,5–trisphosphate (IP3) and diacylglycerol (DAG) (Lieberherr et al. 1993). This was mediated through cell surface receptors for estradiol coupled to phospholipase C. In Chinese hamster ovary (CHO) cells transfected with ERα or ERβ, estrogen binding activated Gαq and Gαs proteins and rapidly stimulated corresponding IP3 production and adenylate cyclase activity (Razandi et al. 1999).