G-protein coupled estrogen receptor 1 (GPER) also known as the membrane estrogen receptor (mER) or G-protein coupled receptor 30 (GPR30) is a G protein-coupled receptor

G protein-coupled receptor

G protein-coupled receptors , also known as seven-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptor, and G protein-linked receptors , comprise a large protein family of transmembrane receptors that sense molecules outside the cell and activate inside signal...

 that in humans is encoded by the GPER gene

Gene

A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

. GPR30 is an integral membrane protein

Integral membrane protein

An integral membrane protein is a protein molecule that is permanently attached to the biological membrane. Proteins that cross the membrane are surrounded by "annular" lipids, which are defined as lipids that are in direct contact with a membrane protein...

 with high affinity for estrogen

Estrogen

Estrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...

.

Function

This protein is a member of the rhodopsin

Rhodopsin

Rhodopsin, also known as visual purple, is a biological pigment of the retina that is responsible for both the formation of the photoreceptor cells and the first events in the perception of light. Rhodopsins belong to the G-protein coupled receptor family and are extremely sensitive to light,...

-like family of G protein-coupled receptor

G protein-coupled receptor

G protein-coupled receptors , also known as seven-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptor, and G protein-linked receptors , comprise a large protein family of transmembrane receptors that sense molecules outside the cell and activate inside signal...

s and is a multi-pass membrane protein that localizes to the endoplasmic reticulum

Endoplasmic reticulum

The endoplasmic reticulum is an organelle of cells in eukaryotic organisms that forms an interconnected network of tubules, vesicles, and cisternae...

. The protein binds estrogen

Estrogen

Estrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...

, resulting in intracellular calcium mobilization and synthesis of phosphatidylinositol (3,4,5)-trisphosphate

Phosphatidylinositol (3,4,5)-trisphosphate

Phosphatidylinositol -triphosphate , abbreviated PIP3, is the product of the class I phosphoinositide 3-kinases phosphorylation on phosphatidylinositol -bisphosphate .-Discovery:...

 in the nucleus. This protein therefore plays a role in the rapid nongenomic signaling events widely observed following stimulation of cells and tissues with estrogen. Alternate transcriptional splice variants which encode the same protein have been characterized. The distribution of GPR30 is well established in the rodent, with high expression observed in the hypothalamus, pituitary gland, adrenal medulla, kidney medulla and developing follicles of the ovary.

Animal studies

Female GPR30 knockout mice

Knockout mouse

A knockout mouse is a genetically engineered mouse in which researchers have inactivated, or "knocked out," an existing gene by replacing it or disrupting it with an artificial piece of DNA...

 display hyperglycemia

Hyperglycemia

Hyperglycemia or Hyperglycæmia, or high blood sugar, is a condition in which an excessive amount of glucose circulates in the blood plasma. This is generally a glucose level higher than 13.5mmol/l , but symptoms may not start to become noticeable until even higher values such as 15-20 mmol/l...

 and impaired glucose tolerance, reduced body growth, and increased blood pressure

Blood pressure

Blood pressure is the pressure exerted by circulating blood upon the walls of blood vessels, and is one of the principal vital signs. When used without further specification, "blood pressure" usually refers to the arterial pressure of the systemic circulation. During each heartbeat, BP varies...

. Male GPR30 knockout mice are observed to have increased growth, body fat, increased osteoblast

Osteoblast

Osteoblasts are mononucleate cells that are responsible for bone formation; in essence, osteoblasts are specialized fibroblasts that in addition to fibroblastic products, express bone sialoprotein and osteocalcin.Osteoblasts produce a matrix of osteoid, which is composed mainly of Type I collagen...

 function (mineralization) resulting in higher bone mineral density and trabecular bone volume, and persistent growth plate activity resulting in longer bones.

Clinical significance

GPR30 plays an important role in development of tamoxifen

Tamoxifen

Tamoxifen is an antagonist of the estrogen receptor in breast tissue via its active metabolite, hydroxytamoxifen. In other tissues such as the endometrium, it behaves as an agonist, hence tamoxifen may be characterized as a mixed agonist/antagonist...

resistance in breast cancer cells.