Steroid hormone receptor



Steroid hormone receptors are transcription factors. 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

Structure

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

  1. Variable domain: It begins at the N-terminal and is the most variable domain between the different receptors.
  2. DNA binding domain: This centrally located highly conserved DNA binding domain (DBD) consists of two non-repetitive globular motifs (PDB: 1HCQ) where zinc is coordinated with four zinc fingers.[1] This region controls which gene will be activated. On DNA it interacts with the hormone response element (HRE).
  3. Hinge region: This area controls the movement of the receptor to the nucleus.
  4. Hormone binding domain: The moderately conserved 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.[2]

Steroid hormone receptors can also function outside of the nucleus and couple to cytoplasmic signal transduction proteins such as PI3k and Akt kinase.[3]

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 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 elements (HRE) for steroid hormone receptors are DNA sequences with the structure of a pair of palindrome or tandem sequences often separated by three nucleotides. 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.[4]

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

References

  1. ^ Evans, R.M. The steroid and thyroid hormone receptor superfamily. Science 240:889-895. 1988. PMID 3283939.
  2. ^ 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.
  3. ^ 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.
  4. ^ 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
v • d • e
intracellular receptors
(1) Basic domains
(1.1) Basic leucine zipper (bZIP) Activating transcription factor (1, 2, 3, 4, 5, 6) • AP-1 (CREB (1, 3) • GABPA • MAF (B, F, G, K) • NRL • NRF1 • XBP1
(1.2) Basic helix-loop-helix (bHLH) ATOH1 • Myogenic regulatory factors (MyoD, Myogenin, MYF5, MYF6) • NEUROD1 • Twist • USF1
(1.3) bHLH-ZIP Myc • MITF • SREBP (1, 2)
(1.6) Basic helix-span-helix (bHSH) AP-2
(2) Zinc finger
DNA-binding domains
(2.1) Nuclear receptor (Cys4) subfamily 1 (Thyroid hormone (α, β), CAR, FXR, DAX1, SHP)
(2.2) Other Cys4 GATA (1, 2, 3, 4, 5, 6)
(2.3) Cys2His2 268, 281, 350) • Zbtb7 (7A) • ZBT (16, 17, 33)
(2.4) Cys6 HIVEP1
(3) Helix-turn-helix
domains
(3.1) Homeo domain ARX • 3/4, 6, 7)
(3.2) Paired box 6, 7, 8, 9)
(3.3) winged helix P3)
(3.4) Heat Shock Factors HSF1
(3.5) Tryptophan clusters ELF (4, 5) • Interferon regulatory factors (1, 2, 3, 4, 5, 6, 7, 8) • MYB
(3.6) TEA domain transcriptional enhancer factor 1, 2
(4) β-Scaffold factors with
minor groove contacts
(4.1) Rel homology region NF-κB (NFKB1, NFKB2, REL, RELA, RELB) • NFAT (5, C1, C2, C3, C4)
(4.2) STAT 6)
(4.3) p53 p53
(4.4) MADS box Mef2 (A, B, C, D) • SRF
(4.7) High mobility group HNF (1A, 1B) • LEF1 • SRY • SSRP1
(4.10) Cold-shock domain CSDA
(4.11) Runt CBF (RUNX1, RUNX2, RUNX3)
(0) Other
transcription factors
(0.2) HMGI(Y) HMGA (1, 2)
(0.3) Pocket domain Rb • RBL1 • RBL2
(0.6) Miscellaneous ARID (1A, 1B, 2, 3A, 3B, 4A) • CAP • Rho/Sigma • R-SMAD
 
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Steroid_hormone_receptor". A list of authors is available in Wikipedia.