Steroid hormone receptor
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'''Steroid hormone receptors''' are [[intracellular receptor]]s (typically [[cytoplasm]]ic) that perform [[signal transduction]] for [[steroid hormone]]s. Steroid [[hormone]] [[receptor (biochemistry)|receptors]] are part of the [[nuclear receptor]] family that include a group of homologous structured receptors (type II receptors) that bind to non-steroid [[ligand]]s such as [[thyroid hormone]]s and [[vitamin A]], as well as to [[vitamin D]], and [[orphan receptor]]s. All these receptors are [[transcription factor]]s. Depending upon the steroid hormone that they bind, they are either located in the [[cytosol]] and move to the [[cell nucleus]] upon activation, or spend their life in the nucleus waiting for the the steroid hormone to enter and activate them. This uptake into the nucleus has to do with Nuclear Localization Signals (NLS) found in a region of the receptor. In most cases this signal is covered up by heat shock proteins which bind the receptor until the hormone is present. Upon binding by the hormone the receptor undergoes a conformational change, the heat shock proteins come off, and the receptor together the with bound hormone enter the nucleus to act upon transcription.
== Types ==
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* Type I Receptors
** [[Sex hormone receptor]]s ([[sex hormone]]s)
*** [[Androgen receptor]]
*** [[Estrogen receptor]]
*** [[Progesterone receptor]]
** [[Glucocorticoid receptor]] ([[glucocorticoid]]s)
** [[Mineralocorticoid receptor]] ([[mineralocorticoids]])
* Type II Receptors
** [[Vitamin A receptor]] ([[Vitamin A]])
** [[Vitamin D receptor]] ([[Vitamin D]])
** [[Retinoid receptor]]
** [[Thyroid hormone receptor]]
* [[Orphan receptor]]s
== Structure ==
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 ([[Protein Data Bank|PDB]]: [http://www.rcsb.org/pdb/cgi/explore.cgi?pid=279521117229963&pdbId=1HCQ 1HCQ]) where zinc is coordinated with four [[cysteine]] and no [[histidine]] residues. Their secondary and tertiary structure is distinct from that of classic [[zinc finger]]s.<ref>Evans, R.M. ''The steroid and thyroid hormone receptor superfamily''. Science 240:889-895. 1988. PMID 3283939.</ref> 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 sequences capable of binding chaperones and parts of dimerization interfaces. Such receptors are closely related to [[Chaperone (protein)|chaperone]]s (namely heat shock proteins [[hsp90]] and [[hsp56]]), which are required to maintain their inactive (but receptive) cytoplasmic [[conformation]]. At the end of this domain is the C-terminal. The terminal connects the molecule to its pair in the homodimer or heterodimer. It may affect the magnitude of the response.
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 receptors have no hsp, and in contrast to the classical type I receptor are located in the cell nucleus.
There is some evidence that certain steroid hormone receptors can extend through lipid bilayer membranes at the surface of cells and might be able to interact with hormones that remain outside of cells.<ref>Luconi M, Francavilla F, Porazzi I, Macerola B, Forti G, Baldi E. ''Human spermatozoa as a model for studying membrane receptors mediating rapid nongenomic effects of progesterone and estrogens.'' Steroids 2004;69:553-9. PMID 15288769.</ref>
Steroid hormone receptors can also function outside of the nucleus and couple to cytoplasmic signal transduction proteins such as PI3k and Akt kinase.<ref>Aquila S, Sisci D, Gentile M, Middea E, Catalano S, Carpino A, Rago V, Ando S. ''Estrogen receptor (ER)alpha and ER beta are both expressed in human ejaculated spermatozoa: evidence of their direct interaction with phosphatidylinositol-3-OH kinase/Akt pathway.'' J Clin Endocrinol Metab 2004;89:1443-51. [[PMID]] 15001646.</ref>
== Functioning ==
Free (that is, unbound) steroids enter the cell cytoplasm and interact with their receptor. In this process heat shock protein is dissociated, and the activated receptor-ligand complex is translocated into the nucleus.
After binding to the [[ligand]] (steroid hormone), steroid receptors often form [[dimer]]s. In the nucleus the complex acts as [[transcription factor]]s, augmenting or suppressing [[Transcription (genetics)|transcription]] of particular [[gene]]s by its action on DNA. As a result [[messenger RNA]] is produced that exits the nucleus and interacts with [[ribosomes]]. There, after [[translation (genetics)|translation]] of the genetic message, specific proteins are produced. These specific proteins perform a biological task.
Type II receptors are located in the nucleus. Thus their ligands pass through the cell wall and cytoplasm and enter the nucleus, where they activated the receptor without release of hsp. The activated receptor interacts with the hormone response element, and the transcription process is initiated as with type I receptors.
== Action on DNA ==
The [[hormone response element]]s (HRE) for steroid hormone receptors are DNA sequences with the structure of a pair of [[palindrome]] or [[tandem]] sequences often separated by three [[nucleotide]]s. These elements resemble each other in their length and arrangement but differ in their sequences.
A given hormone-receptor complex's ability to cause a change in the expression of the gene it regulates depends on the specific HRE sequence, the distance of HRE from the gene and the number of HRE affecting the gene.<ref>David L. Nelson, Michael M. Cox. ''Lehninger Principles of Biochemistry, Third Edition''. W.H. Freeman & Company; 3rd Bk&CD edition (May 1, 2000). ISBN 1-57259-931-6</ref>
The biological response is influenced by the amount of hormones available, the available receptor population, the dissociation rate of the hormone-receptor complex with the specific DNA site, and the replenishment of the receptor population.
== See also ==
* [[Receptor (biochemistry)|Receptors]]
* [[Nuclear receptor]]
== References ==
<references/>
==External links==
* [http://www.neurosci.pharm.utoledo.edu/MBC3320/steroids.htm#receptors MBC 3320 Steroid hormones and receptors], by Dr. William S. Messer, updated on Monday, April 3, 2000 at 6:05 p.m.
* [http://www.sbs.utexas.edu/dharma/TSM%20lectures/Steroid%20Hormone%20Receptor%20Signaling.doc Steroid Hormone Receptor Signaling]. Transcript from Ed. Ralph, A. Bradshaw and Edward A. Dennis: ''Handbook of Cell Signaling''. Academic press, CA, chapter 275. ISBN 0-12-124546-2. Retrieved on May 25, 2005 at 7:49 a.m. (UTC).
* {{MeshName|Steroid+Receptors}}
{{Transcription factors|g2}}
[[Category:Intracellular receptors]]
[[de:Steroidrezeptor]]
[[fr:Récepteur des stéroïdes]]