Estrogen-related receptor gamma

Estrogen-related receptor gamma (ERR-gamma), also known as NR3B3 (nuclear receptor subfamily 3, group B, member 3), is a is_associated_with::nuclear receptor that in humans is encoded by the ESRRG (EStrogen Related Receptor Gamma) is_associated_with::gene. It behaves as a constitutive activator of transcription.

This protein is a member of nuclear hormone receptor family of is_associated_with::steroid hormone receptors. No physiological activating ligand is known for this is_associated_with::orphan receptor, but is_associated_with::4-hydroxytamoxifen and is_associated_with::diethylstilbestrol act as is_associated_with::inverse agonists and deactivate ESRRG. It also seems to be the target of is_associated_with::bisphenol A (see below).

Bisphenol A binding
There is evidence that bisphenol A functions as an is_associated_with::endocrine disruptor by binding strongly to ERR-γ. BPA as well as its nitrated and chlorinated metabolites seems to binds strongly to ERR-γ (is_associated_with::dissociation constant = 5.5 nM), but not to the is_associated_with::estrogen receptor (ER)., BPA binding to ERR-γ preserves its basal constitutive activity. It can also protect it from deactivation from the is_associated_with::selective estrogen receptor modulator is_associated_with::4-hydroxytamoxifen.

Different expression of ERR-γ in different parts of the body may account for variations in bisphenol A effects. For instance, ERR-γ has been found in high concentration in the is_associated_with::placenta, explaining reports of high bisphenol A accumulation there.