The third class of nuclear receptors (Nuclear, Class 3, Estrogen Receptor-like) includes estrogen and estrogen-related receptors (ER), as well as the 3-ketosteroid receptors (progesterone (PR), androgen (AR), gluco- and mineralocorticoid (GR and MR, respectively) receptors). Estrogen is a key regulator of growth, differentiation and function in a broad range of target tissues, including the male and female reproductive tracts, mammary gland, bone, brain and the cardiovascular system. The biological effects of estrogen are mediated through estrogen receptors α and β (ERα, β). The classical mechanism of activation of ERs depends on ligand binding to the receptors, after which the receptors dimerize and bind to estrogen response elements (EREs) located in the promoters of estrogen-responsive genes. ERs may also regulate gene expression in the absence of DNA-binding by modulating the activities of other transcription factors via protein-protein interactions on DNA. This mechanism is referred to as cross-talk and is common for several nuclear receptors[1].  As the name implies, the family of estrogen receptor-related receptors (ERRs) is a subfamily of the orphan nuclear receptors, which is closely related to the estrogen receptor (ER) family, and comprises three subtypes (ERRα-γ). Sequence analyses comparing all the class 3 NRs have shown that both ERs and ERRs together form the same branch of class 3, which recognizes a specific hormone response element (HRE), whereas the other four steroid receptors (PR, AR, GR, and MR) recognize a different, yet specific HRE, thereby forming another branch[2].
Corticosteroid receptors include mineralocorticoid (MR) and glucocorticoid (GR) receptors. They play a crucial role in the regulation of a variety of physiological processes, including reproduction, metabolism, salt balance, inflammation, and immunity. Cortisol is the principal glucocorticoid that induces the transcriptional activities of both the GR and MR, whereas the mineralocorticoid aldosterone also activates only MR, but not GR[3].
The MR belongs to the cytosolic receptor family where the ligand diffuses into cells, interacts with the receptor and results in a signal transduction affecting specific gene expression in the nucleus. The GR, however, upon activation may up-regulate the expression of anti-inflammatory proteins in the nucleus or repress the expression of pro-inflammatory proteins in the cytosol by preventing the translocation of other transcription factors from the cytosol into the nucleus. In the absence of hormone, the MR and GR reside in the cytosol complexed with a variety of proteins including heat shock protein 70 and 90 (hsp70, hsp90), high-mobility group box proteins (HMGBs), and FKBP52 (FK506-binding protein 52)[4].