GPER

G protein-coupled estrogen receptor 1 (GPER), formerly referred to as G protein-coupled receptor 30 (GPR30), is a is_associated_with::G protein-coupled receptor that in humans is encoded by the GPER is_associated_with::gene. GPER is an is_associated_with::integral membrane protein with high affinity for is_associated_with::estradiol, though not for other is_associated_with::endogenous is_associated_with::estrogens, such as is_associated_with::estrone or is_associated_with::estriol, nor for other endogenous steroids, including is_associated_with::progesterone, is_associated_with::testosterone, and is_associated_with::cortisol. However, GPER does show high affinity for is_associated_with::aldosterone.

Function
This protein is a member of the is_associated_with::rhodopsin-like family of is_associated_with::G protein-coupled receptors and is a multi-pass membrane protein that localizes to the is_associated_with::endoplasmic reticulum. The protein binds estradiol, resulting in intracellular calcium mobilization and synthesis of is_associated_with::phosphatidylinositol (3,4,5)-trisphosphate in the nucleus. This protein therefore plays a role in the rapid nongenomic signaling events widely observed following stimulation of cells and tissues with estradiol. Alternate transcriptional splice variants that encode the same protein have been characterized. The distribution of GPER 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 GPER knockout mice display is_associated_with::hyperglycemia and impaired is_associated_with::glucose tolerance, reduced body growth, and increased is_associated_with::blood pressure. Male GPER knockout mice are observed to have increased growth, body fat, increased is_associated_with::osteoblast function (mineralization) resulting in higher bone mineral density and trabecular bone volume, and persistent growth plate activity resulting in longer bones.

GPER is expressed in the is_associated_with::breasts, and activation by estradiol produces is_associated_with::cell proliferation in both normal and malignant is_associated_with::breast is_associated_with::epithelial tissue. However, GPER knockout mice show no overt mammary is_associated_with::phenotype, unlike ERα knockout mice, but similarly to ERβ knockout mice. This indicates that although GPER and ERβ play a modulatory role in is_associated_with::breast development, ERα is the main receptor responsible for estrogen-mediated breast tissue growth.

Clinical significance
GPER plays an important role in development of is_associated_with::tamoxifen resistance in breast cancer cells.