Steroid hormone receptor - wikipedia Steroid hormone receptor 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. Contents 1 Types 1.1 Nuclear receptors 1.1. 1 Structure 1.1. 2 Mechanism of action 1.1. 2.1 Genomic 1.1. 2.2 Non-genomic 1.2 Other 1.2. 1 G protein - coupled receptors 1.2. 2 Ion channels 1.2. 3 SHBG / SHBG - R complex 2 See also 3 References 4 External links Types Nuclear receptors Main article : nuclear receptor 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. Nuclear receptors Subfamily 3 : Estrogen Receptor - like Group A : Estrogen receptor ( Sex hormones : Estrogen ) 1 : Estrogen receptor - α ( ERα ; NR3A1, ESR1 ) 2 : Estrogen receptor - β ( ERβ ; NR3A2, ESR2 ) Group C : 3 - Ketosteroid receptors 1 : Glucocorticoid receptor ( GR ; NR3C1 ) ( Cortisol ) 2 : Mineralocorticoid receptor ( MR ; NR3C2 ) ( Aldosterone ) 3 : Progesterone receptor ( PR ; NR3C3, PGR ) ( Sex hormones : Progesterone ) 4 : Androgen receptor ( AR ; NR3C4, AR ) ( Sex hormones : Testosterone ) Structure Intracellular 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 where zinc is coordinated with four cysteine and no histidine residues. Their secondary and tertiary structure is distinct from that of classic zinc fingers. 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 chaperones ( 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. Mechanism of action Genomic 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. 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 dimers. In the nucleus, the complex acts as a transcription factor, augmenting or suppressing transcription particular genes by its action on DNA. Type II receptors are located in the nucleus. Thus, their ligands pass through the cell membrane and cytoplasm and enter the nucleus where they activate 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. Nongenomic The cell membrane aldosterone receptor has shown to increase the activity of the basolateral Na / K ATPase, ENaC sodium channels and ROMK potassium channels of the principal cell in the distal tubule and cortical collecting duct of nephrons ( as well as in the large bowel and possibly in sweat glands ). 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 cells. Steroid hormone receptors can also function outside the nucleus and couple to cytoplasmic signal transduction proteins such as PI3k and Akt kinase. Other A new class of steroid hormone receptors has recently been elucidated and these new receptors are found on the cell membrane. New studies suggest that along with the well documented intracellular receptors that cell membrane receptors are present for several steroid hormones and that their cellular responses are much quicker than the intracellular receptors. G protein - coupled receptors GPCR linked proteins most likely interact with steroid hormones through an amino acid consensus sequence traditionally thought of as a cholesterol recognition and interaction site. About a third of Class A GPCRs contain this sequence. The steroid hormones themselves are different enough from one another that they do not all affect all of the GPCR linked proteins ; however, the similarities between the steroid hormones and between the receptors make plausible the argument that each receptor may respond to multiple steroid hormones or that each hormone could affect multiple receptors. This is contrary to the traditional model of having a unique receptor for each unique ligand. At least four different GPCR - linked proteins are known to respond to steroid hormones. G Protein - Coupled Receptor 30 ( GPR30 ) binds estrogen, Membrane Progestin Receptor ( mPR ) binds progesterone, G Protein - Coupled Receptor Family C Group 6 Member A ( GPRC6A ) binds androgens, and Thyroid Hormone and Trace Amine Associated Receptor 1 ( TAAR1 ) binds Thyroid hormone ( though not technically steroid hormones, thyroid hormones can be grouped here because their receptors belong to the nuclear receptor superfamily ). As an example of the effects of these GPCR - linked proteins consider GPR30. GPR30 binds estrogen, and upon binding estrogen this pathway activates adenylyl cyclase and epidermal growth factor receptor. It results in vasodilation, renoprotection, mammary gland development, etc. Ion channels Neuroactive steroids bind to and modulate the activity of several ion channels including the GABA, NMDA, and sigma receptors. The steroid progesterone has been found to modulate the activity of CatSper ( cation channels of sperm ) voltage - gated Ca channels. Since eggs release progesterone, sperm may use progesterone as a homing signal to swim toward eggs ( chemotaxis ). SHBG / SHBG - R complex Sex hormone - binding globulin ( SHBG ) is thought to mainly function as a transporter and reservoir for the estradiol and testosterone sex hormones. However it has also been demonstrated that SHBG can bind to a cell surface receptor ( SHBG - R ). The SHBG - R has not been completely characterized. A subset of steroids are able to bind to the SHBG / SHBG - R complex resulting in an activation of adenylyl cyclase and synthesis of the cAMP second messenger. Hence the SHBG / SHBG - R complex appears to act as a transmembrane steroid receptor that is capable of transmitting signals to the interior of cells. See also Membrane steroid receptor Nuclear receptor References Jump up ^ Dahlman - Wright K, Cavailles V, Fuqua SA, Jordan VC, Katzenellenbogen JA, Korach KS, Maggi A, Muramatsu M, Parker MG, Gustafsson JA ( Dec 2006 ). `` International Union of Pharmacology. LXIV. Estrogen receptors ''. Pharmacological Reviews. 58 ( 4 ) : 773 -- 81. doi : 10.1124 / pr. 58.4. 8. PMID 17132854. Jump up ^ Lu NZ, Wardell SE, Burnstein KL, Defranco D, Fuller PJ, Giguere V, Hochberg RB, McKay L, Renoir JM, Weigel NL, Wilson EM, McDonnell DP, Cidlowski JA ( Dec 2006 ). `` International Union of Pharmacology. LXV. The pharmacology and classification of the nuclear receptor superfamily : glucocorticoid, mineralocorticoid, progesterone, and androgen receptors ''. Pharmacological Reviews. 58 ( 4 ) : 782 -- 97. doi : 10.1124 / pr. 58.4. 9. PMID 17132855. Jump up ^ PDB : 1HCQ ​ ; Schwabe JW, Chapman L, Finch JT, Rhodes D ( Nov 1993 ). `` The crystal structure of the estrogen receptor DNA - binding domain bound to DNA : how receptors discriminate between their response elements ''. Cell. 75 ( 3 ) : 567 -- 78. doi : 10.1016 / 0092 - 8674 ( 93 ) 90390 - C. PMID 8221895. Jump up ^ Evans RM ( May 1988 ). `` The steroid and thyroid hormone receptor superfamily ''. Science. 240 ( 4854 ) : 889 -- 95. doi : 10.1126 / science. 3283939. PMID 3283939. Jump up ^ Mangelsdorf DJ, Thummel C, Beato M, Herrlich P, Schütz G, Umesono K, Blumberg B, Kastner P, Mark M, Chambon P, Evans RM ( Dec 1995 ). `` The nuclear receptor superfamily : the second decade ''. 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Jump up ^ Herd MB, Belelli D, Lambert JJ ( Oct 2007 ). `` Neurosteroid modulation of synaptic and extrasynaptic GABA ( A ) receptors ''. Pharmacology & Therapeutics. 116 ( 1 ) : 20 -- 34. doi : 10.1016 / j. pharmthera. 2007.03. 007. PMID 17531325. Jump up ^ Hosie AM, Wilkins ME, da Silva HM, Smart TG ( Nov 2006 ). `` Endogenous neurosteroids regulate GABAA receptors through two discrete transmembrane sites ''. Nature. 444 ( 7118 ) : 486 -- 9. doi : 10.1038 / nature05324. PMID 17108970. Jump up ^ Puia G, Santi MR, Vicini S, Pritchett DB, Purdy RH, Paul SM, Seeburg PH, Costa E ( May 1990 ). `` Neurosteroids act on recombinant human GABAA receptors ''. Neuron. 4 ( 5 ) : 759 -- 65. doi : 10.1016 / 0896 - 6273 ( 90 ) 90202 - Q. PMID 2160838. Jump up ^ Wu FS, Gibbs TT, Farb DH ( Sep 1991 ). `` Pregnenolone sulfate : a positive allosteric modulator at the N - methyl - D - aspartate receptor '' ( abstract ). Molecular Pharmacology. 40 ( 3 ) : 333 -- 6. PMID 1654510. Jump up ^ Maurice T, Junien JL, Privat A ( Feb 1997 ). `` Dehydroepiandrosterone sulfate attenuates dizocilpine - induced learning impairment in mice via sigma 1 - receptors ''. Behavioural Brain Research. 83 ( 1 - 2 ) : 159 -- 64. doi : 10.1016 / S0166 - 4328 ( 97 ) 86061 - 5. PMID 9062676. Jump up ^ Strünker T, Goodwin N, Brenker C, Kashikar ND, Weyand I, Seifert R, Kaupp UB ( Mar 2011 ). `` The CatSper channel mediates progesterone - induced Ca2+ influx in human sperm ''. Nature. 471 ( 7338 ) : 382 -- 6. doi : 10.1038 / nature09769. PMID 21412338. Lay summary -- Nature News. Jump up ^ Lishko PV, Botchkina IL, Kirichok Y ( Mar 2011 ). `` Progesterone activates the principal Ca2+ channel of human sperm ''. Nature. 471 ( 7338 ) : 387 -- 91. doi : 10.1038 / nature09767. PMID 21412339. Jump up ^ Rosner W, Hryb DJ, Kahn SM, Nakhla AM, Romas NA ( Mar 2010 ). `` Interactions of sex hormone - binding globulin with target cells ''. 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Transcription factors and intracellular receptors ( 1 ) Basic domains ( 1.1 ) Basic leucine zipper ( bZIP ) Activating transcription factor AATF 5 6 7 AP - 1 c - Fos FOSB FOSL1 FOSL2 JDP2 c - Jun JUNB JunD BACH BATF BLZF1 C / EBP α β γ δ ε ζ CREB L1 CREM DBP DDIT3 GABPA GCN4 HLF MAF NFE L1 L2 L3 NFIL3 NRL NRF XBP1 ( 1.2 ) Basic helix - loop - helix ( bHLH ) ATOH1 AhR AHRR ARNT ASCL1 BHLH 9 ARNTL ARNTL ARNTL2 CLOCK EPAS1 FIGLA HAND HES 5 6 HEY HES1 HIF 1A 3A ID LYL1 MESP2 MXD4 MYCL1 MYCN Myogenic regulatory factors MyoD Myogenin MYF5 MYF6 Neurogenins NeuroD NPAS OLIG Pho4 Scleraxis SIM TAL Twist USF1 ( 1.3 ) bHLH - ZIP AP - 4 MAX MXD3 MITF MNT MLX MXI1 Myc SREBP ( 1.4 ) NF - 1 NFI X SMAD R - SMAD 5 9 I - SMAD 6 7 4 ) ( 1.5 ) RF - X RFX 5 6 ANK ( 1.6 ) Basic helix - span - helix ( bHSH ) AP - 2 α β γ δ ε ( 2 ) Zinc finger DNA - binding domains ( 2.1 ) Nuclear receptor ( Cys ) subfamily 1 Thyroid hormone α β CAR FXR LXR α β PPAR α β / δ γ PXR RAR α β γ ROR α β γ Rev - ErbA α β VDR subfamily 2 COUP - TF ( I II Ear - 2 HNF4 α γ PNR RXR α β γ Testicular receptor TLX subfamily 3 Steroid hormone Androgen Estrogen α β Glucocorticoid Mineralocorticoid Progesterone Estrogen related α β γ subfamily 4 NUR NGFIB NOR1 NURR1 subfamily 5 LRH - 1 SF1 subfamily 6 GCNF subfamily 0 DAX1 SHP ( 2.2 ) Other Cys GATA 5 6 MTA TRPS1 ( 2.3 ) Cys His General transcription factors TFIIA TFIIB TFIID TFIIE TFIIF TFIIH 2I 3A 3C1 3C2 ATBF1 BCL 6 11A 11B CTCF E4F1 EGR ERV3 GFI1 GLI - Krüppel family REST S1 S2 YY1 HIC HIVEP IKZF ILF KLF 5 6 7 8 9 10 11 12 13 14 15 17 MTF1 MYT1 OSR1 PRDM9 SALL SP 7 8 TSHZ3 WT1 Zbtb7 7A 7B ZBTB 11 16 17 20 32 33 40 zinc finger 7 9 10 19 22 24 33B 34 35 41 43 44 51 74 143 146 148 165 202 217 219 238 239 259 267 268 281 295 300 318 330 346 350 365 366 384 423 451 452 471 593 638 644 649 655 ( 2.4 ) Cys HIVEP1 ( 2.5 ) Alternating composition AIRE DIDO1 GRLF1 ING JARID 1A 1B 1C 1D JMJD1B ( 2.6 ) WRKY WRKY ( 3 ) Helix - turn - helix domains ( 3.1 ) Homeodomain ARX CDX CRX CUTL1 DBX DLX 5 EMX EN FHL HESX1 HHEX HLX Homeobox A1 A2 A3 A4 A5 A7 A9 A10 A11 A13 B1 B2 B3 B4 B5 B6 B7 B8 B9 B13 C4 C5 C6 C8 C9 C10 C11 C12 C13 D1 D3 D4 D8 D9 D10 D11 D12 D13 HOPX IRX 5 6 MKX LMX 1A 1B MEIS MEOX2 MNX1 MSX NANOG NKX 2 - 1 2 - 2 2 - 3 2 - 5 3 - 1 3 - 2 6 - 1 6 - 2 NOBOX PBX PHF 6 8 10 16 17 20 21A PHOX 2A 2B PITX POU domain PIT - 1 BRN - 3 : A Octamer transcription factor : 1 3 / 4 6 7 11 OTX PDX1 SATB2 SHOX2 SIX 5 VAX1 ZEB ( 3.2 ) Paired box PAX 5 6 7 8 9 PRRX RAX ( 3.3 ) Fork head / winged helix E2F 5 FOX proteins A1 A2 A3 C1 C2 D3 D4 E1 E3 F1 G1 H1 I1 J1 J2 K1 K2 L2 M1 N1 N3 O1 O3 O4 P1 P2 P3 P4 ( 3.4 ) Heat shock factors HSF ( 3.5 ) Tryptophan clusters ELF 5 EGF ELK ERF ETS ERG SPIB ETV 5 6 FLI1 Interferon regulatory factors 5 6 7 8 MYB MYBL2 ( 3.6 ) TEA domain transcriptional enhancer factor ( 4 ) β - Scaffold factors with minor groove contacts ( 4.1 ) Rel homology region NF - κB NFKB1 NFKB2 REL RELA RELB NFAT C1 C2 C3 C4 5 ( 4.2 ) STAT STAT 5 6 ( 4.3 ) p53 p53 TBX 5 19 21 22 TBR1 TBR2 TFT MYRF TP63 ( 4.4 ) MADS box Mef2 SRF ( 4.6 ) TATA - binding proteins TBP TBPL1 ( 4.7 ) High - mobility group BBX HMGB HMGN HNF 1A 1B LEF1 SOX 5 6 8 9 10 11 12 13 14 15 18 21 SRY SSRP1 TCF TOX ( 4.9 ) Grainyhead TFCP2 ( 4.10 ) Cold - shock domain CSDA YBX1 ( 4.11 ) Runt CBF CBFA2T2 CBFA2T3 RUNX1 RUNX2 RUNX3 RUNX1T1 ( 0 ) Other transcription factors ( 0.2 ) HMGI ( Y ) HMGA HBP1 ( 0.3 ) Pocket domain Rb RBL1 RBL2 ( 0.5 ) AP - 2 / EREBP - related factors Apetala 2 EREBP B3 ( 0.6 ) Miscellaneous ARID 1A 1B 3A 3B 4A CAP IFI 16 35 MLL T1 MNDA NFY Rho / Sigma see also transcription factor / coregulator deficiencies Nuclear receptor modulators AhR Agonists : Arachidonic acid metabolites ( e.g., lipoxin A4, prostaglandin G2 ) Dietary carotenoids Flutamide Halogenated aromatic hydrocarbons ( e.g., polychlorinated dibenzodioxins ( e.g., TCDD ), dibenzofurans, biphenyls ) Modified low - density lipoproteins Polycyclic aromatic hydrocarbons ( e.g., 3 - methylcholanthrene, benzo ( a ) pyrene, benzanthracenes, benzoflavones ( e.g., beta - naphthoflavone ) ) Tapinarof Tetrapyroles ( e.g., bilirubin ) Tryptophan derivatives ( e.g., indigo dye, indirubin ) Antagonists : 7 - Ketocholesterol CAR See here instead. ERR ERRα Agonists : 6, 3 ′, 4 ′ - Trihydroxyflavone Biochanin A Cholesterol Daidzein Genistein Antagonists : Diethylstilbestrol XCT - 790 ERRβ Agonists : DY - 131 ( GSK - 9089 ) GSK - 4716 ( GW - 4716 ) Antagonists : 4 - Hydroxytamoxifen ( afimoxifene ) Diethylstilbestrol ERRγ Agonists : Bisphenol A DY - 131 ( GSK - 9089 ) GSK - 4716 ( GW - 4716 ) Antagonists : 4 - Hydroxytamoxifen ( afimoxifene ) Diethylstilbestrol FXR Agonists : Bile acids Cafestol Chenodeoxycholic acid Fexaramine GW - 4064 Obeticholic acid Antagonists : Guggulsterone LXR Agonists : 22R - Hydroxycholesterol 24S - Hydroxycholesterol 27 - Hydroxycholesterol Cholestenoic acid DMHCA GW - 3965 Hypocholamide T - 0901317 Antagonists : Efavirenz PPAR See here instead. PXR See here instead. Retinoid See here instead. SHR AR See here instead. ER See here instead. PR See here instead. GR See here instead. MR See here instead. THR See here instead. VDR See here instead. See also Receptor / signaling modulators Leukotriene signaling modulators Prostanoid signaling modulators Retrieved from `` https://en.wikipedia.org/w/index.php?title=Steroid_hormone_receptor&oldid=824235292 '' Categories : Intracellular receptors Talk Contents About Wikipedia Deutsch Español Français Polski Svenska Edit links This page was last edited on 6 February 2018, at 03 : 19. Text is available under the Creative Commons Attribution - ShareAlike License ; additional terms may apply. By using this site, you agree to the Terms of Use and Privacy Policy. Wikipedia ® is a registered trademark of the Wikimedia Foundation, Inc., a non-profit organization. About Wikipedia

Question: where are the receptors for steroid hormones located
Answer: nucleus