Steroid receptors

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.

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.

Intracellular steroid hormone receptors share a common structure of four units that are functionally homologous, so-called "domains":

Depending on their mechanism of action and subcellular distribution, nuclear receptors may be classified into at least two classes. Nuclear receptors that bind steroid hormones are all classified as type I receptors. Only type I receptors have a heat shock protein (HSP) associated with the inactive receptor that will be released when the receptor interacts with the ligand. Type I receptors may be found in homodimer or heterodimer forms. Type II nuclear receptors have no HSP, and in contrast to the classical type I receptor are located in the cell nucleus.

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