(1) The putative Gq-coupled membrane oestrogen receptor (mER) is a G-protein coupled receptor linked to Gαq/11 protein. Oestrogen binding activates the Gαq/11 (2) which in turn activates (+) phospholipase C (PLC) and initiates the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2). PLC hydrolyzes PIP2 into diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP3). (3) DAG activates protein kinase Cδ (PKCδ) which activates adenylate cyclase VII (AC VII). (4) AC VII increases cAMP production subsequently stimulating protein kinase A (PKA), which through phosphorylation uncouples the inhibitory GABAB and μ-opioid receptors from activation of G-protein coupled inwardly rectifying K+ channels (GIRK) channels. (5) Activation of PKA will also phosphorylate cAMP-response element binding protein (pCREB) and control gene expression through the cAMP response element (CRE). (6) IP3 produced from the hydrolysis of PIP2 activates Ca2+ release from the endoplasmic reticulum that can activate calcium-dependent signalling. (7) Oestradiol will also bind to nuclear receptors and activate oestrogen response element (ERE)-dependent transcription. E2, 17β-oestradiol.