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From Proteopedia

Structure

The steroid hormone receptors have five or six which are encoded by eight to nine exons. The receptors have three major functional domains. These domains include the variable N-terminus which confers immunogenicity, a central DNA-binding domain with two distinct zinc fingers that allow for the receptor to directly interact with the DNA, and the ligand-binding domain. In addition, there are both hydrophobic and regions within the molecule.

Function

Steroid Hormone receptors overlook and control gene expression, the rate of cellular reproduction, and specialization in eukaryotes. The receptors do so by turning genes controlled by particular promoters on or off as steroid molecules (hormones) bind to them. Steroid hormone receptors therefore serve as transcription factors containing zinc fingers which are repeated structural units.

The estrogen receptor (ER) is found in the heat shock protein complex found in the nucleus. When the ligand binds to the ER, it undergoes a conformational change which displaces the heat shock protein complex allowing cofactors to bind and facilitate the receptor's interaction with desired genes. When the oestrogen ligand is present, the oestrogen receptor regulates gene expression by either recognizing and binding to the DNA palindromic estrogen response element sequence (ERE) or by interacting with other transcription factors.

In terms of ligand-independent activity, the ER uses many different intracellular signalling pathways which use either the phosphorylation of the ER by protein kinases or regulation of the ER-bound cofactors to produce various cell and tissue specific oestrogenic responses. For example, the activation of the epidermal growth factor (EGF) receptor leads to ER𝛂 phosphorylation through the mitogen-activated protein kinase (MAPK) pathway which enhances the ER interaction with the steroid receptor co activator, thereby affecting ligand binding. Feedback also occurs where oestrogen activates MAPK pathway which activates the ER and amplifies the pathway signal.

Interactions

Steroid hormone receptors regulate gene transcription through various interaction including binding to the hormone, binding to itself to form a homodimer, binding to its response element, or binding to other protein cofactors. Examples of molecules for steroid hormone receptors include aldosterone, estrogen, the thyroid hormone T3, calcitriol, the active form of vitamin D, and retinol.

Interaction Location

The receptors perform their interactions within the nucleus independent of the heat shock protein complex in order to control gene expression.

Origin

48 steroid hormone and nuclear receptor genes have been revealed in humans. The highly conserved DNA binding domains and the ligand binding domains indicate that the steroid hormone receptors share a common ancestral molecule.

References

4aa6. (n.d.). Retrieved February 15, 2017, from http://www.proteopedia.org/wiki/index.php/4aa6

Oestrogen Receptors. (n.d.). Retrieved February 15, 2017, from https://www.ebi.ac.uk/interpro/potm/2003_4/Page_2.htm

The Steroid Hormone Receptors | GLOWM. (n.d.). Retrieved February 15, 2017, from https://www.glowm.com/section_view/heading/The%20Steroid%20Hormone%20Receptors/item/280

Steroid Hormone Receptors and their Response Elements. (n.d.). Retrieved February 15, 2017, from http://www.biology-pages.info/S/SteroidREs.html