Steroid hormone receptors are found in the nucleus, cytosol, and also on the plasma membrane of target cells. They are generally intracellular receptors (typically cytoplasmic or nuclear) and initiate signal transduction for steroid hormones which lead to changes in gene expression over a time period of hours to days. The best studied steroid hormone receptors are members of the nuclear receptor subfamily 3 (NR3) that include receptors for estrogen (group NR3A) and 3-ketosteroids (group NR3C). In addition to nuclear receptors, several G protein-coupled receptors and ion channels act as cell surface receptors for certain steroid hormones. Types Nuclear receptors Steroid receptors of the nuclear receptor family are all transcription factors. Depending upon the type of receptor, they are either located in the cytosol and move to the cell nucleus upon activation, or remain in the nucleus waiting for the steroid hormone to enter and activate them. This uptake into the nucleus is facilitated by nuclear localization signal (NLS) found in the hinge region of the receptor. This region of the receptor is covered up by heat shock proteins (HSPs) which bind the receptor until the hormone is present. Upon binding by the hormone the receptor undergoes a conformational change releasing the HSP, and the receptor together with the bound hormone enter the nucleus to act upon transcription. Nuclear receptors Subfamily 3: Estrogen Receptor-like Group A: Estrogen receptor (Sex hormones: Estrogen) 1: Estrogen receptor-α (ERα; NR3A1, ) 2: Estrogen receptor-β (ERβ; NR3A2, ) Group C: 3-Ketosteroid receptors 1: Glucocorticoid receptor (GR; ) (Cortisol) 2: Mineralocorticoid receptor (MR; ) (Aldosterone) 3: Progesterone receptor (PR; NR3C3, ) (Sex hormones: Progesterone) 4: Androgen receptor (AR; NR3C4, ) (Sex hormones: Testosterone) Structure Intracellular steroid hormone receptors share a common structure of four units that are functionally homologous, so-called "domains": Variable domain: It begins at the N-terminal and is the most variable domain between the different receptors. DNA binding domain: This centrally located highly conserved DNA binding domain (DBD) consists of two non-repetitive globular motifs where zinc is coordinated with four cysteine and no histidine residues. Their secondary and tertiary structure is distinct from that of classic zinc fingers. This region controls which gene will be activated. On DNA it interacts with the hormone response element (HRE). Hinge region: This area controls the movement of the receptor to the nucleus. Hormone binding domain: The moderately conserved ligand-binding domain (LBD) can include a nuclear localization signal, amino-acid