Sierra Acai Company
Sierra Acai Company
Open 7 Days a Week
MonaVie Independent Distributor
Distributor Training
Shop Online
Enroll Now
Buy Wholesale and maintain an Active status for 2 months and we will refund your $39 Distributor Fee
Friends
Buy Wholesale and maintain an Active status for 2 months and we will refund your $39 Distributor Fee
14-September-2008 18:02:42 - FSH-receptor Follicle stimulating hormone receptor PDB rendering based on 1xwd. Available structures: 1xwd Identifiers Symbols FSHR; FSHRO; LGR1; MGC141667; MGC141668; ODG1 External IDs OMIM: 136435 MGI: 95583 HomoloGene: 117 Gene ontology Molecular function: receptor activity follicle-stimulating hormone receptor activity protein binding Cellular component: plasma membrane integral to membrane Biological process: signal transduction G-protein coupled receptor protein signaling pathway spermatogenesis female gamete generation female gonad development RNA expression pattern More reference expression data Orthologs Human Mouse Entrez 2492 14309 Ensembl ENSG00000170820 ENSMUSG00000032937 Uniprot P23945 P35378 Refseq NM_000145 mRNA NP_000136 protein NM_013523 mRNA NP_038551 protein Location Chr 2: 49.04 - 49.24 Mb Chr 17: 88.89 - 89.11 Mb Pubmed search 1 2 The follicle stimulating hormone receptor or FSH-receptor FSHR is a transmembrane receptor that interacts with the follicle stimulating hormone FSH and represents a G protein-coupled receptor GPCR. Its activation is necessary for the hormonal functioning of FSH. FSHRs are found in the ovary, testis, and uterus. Contents 1 FSHR gene 2 Receptor structure 3 Ligand binding and signal transduction 3.1 Phosphorylation by cAMP-dependent protein kinases 4 Action 5 Receptor regulation 5.1 Upregulation 5.2 Desensitization 5.3 Downregulation 5.4 Modulators 6 FSHR abnormalities 7 History 8 See also 9 References 10 Further reading 11 External links FSHR gene The gene for the FSHR is found on chromosome 2 p21 in humans. The gene sequence of the FSHR consists of about 2,080 nucleotides.1 The seven transmembrane α-helix structure of a G protein-coupled receptor such as FSHR The seven transmembrane α-helix structure of a G protein-coupled receptor such as FSHR Receptor structure The FSHR consists of 695 amino acids and has a molecular mass of about 76 kDa.1 Like other GPCRs, the FSH-receptor possess seven membrane-spanning domains or transmembrane helices. The extracellular domain of the receptor is glycosylated. The transmembrane domain contains two highly conserved cysteine residues which build disulfide bonds to stabilize the receptor structure. A highly conserved Asp-Arg-Tyr triplet motif is present and may be of importance to transmit the signal. The C-terminal domain is intracellular and brief, rich in serine and threonine residues for possible phosphorylation. Ligand binding and signal transduction Upon binding FSH externally to the membrane, a transduction of the signal takes place that activates the G protein that is bound to the receptor internally. With FSH attached, the receptor shifts conformation and thus mechanically activates the G protein, which detaches from the receptor and activates the cAMP system. It is believed that a receptor molecule exists in a conformational equilibrium between active and inactive states. The binding of FSH to the receptor shifts the equilibrium between active and inactive receptors. FSH and FSH-agonists shift the equilibrium in favor of active states; FSH antagonists shift the equilibrium in favor of inactive states. For a cell to respond to FSH only a small percentage ~1% of receptor sites need to be activated. Phosphorylation by cAMP-dependent protein kinases Cyclic AMP-dependent protein kinases protein kinase A are activated by the signal chain coming from the G protein that was activated by the FSH-receptor via adenylate cyclase and cyclic AMP cAMP. These protein kinases are present as tetramer with two regulatory units and two catalytic units. Upon binding of cAMP to the regulatory units, the catalytic units are released and initiate the phosphorylation of proteins leading to the physiologic action. The cyclic AMP-regulatory dimers are degraded by phosphodiesterase and release 5'AMP. DNA in the cell nucleus binds to phosphorylated proteins through the cyclic AMP response element CRE which results in the activation of genes.1 The signal is amplified by the involvement of cAMP and the resulting phosphorylation. The process is modified by prostaglandins. Other cellular regulators are participate are the intracellular calcium concentration modified by phospholipase, nitric acid, and other growth factors. The FSH receptor can also activate the extracellular signal-regulated kinases ERK. 2 In a feedback mechanism, these activated kinases phosphorylate the receptor. The longer the receptor remains active, the more kinases are activated, the more receptors are phosphorylated. Action In the ovary, the FSH receptor is necessary for follicular development and expressed on the granulosa cells.1 In the male the FSH receptor has been identified on the Sertoli cells that are critical for spermatogenesis.3 The FSHR is expressed during the luteal phase in the secretory endometrium of the uterus.4 Receptor regulation Upregulation Upregulation refers to the increase in the number of receptor site on the membrane. Estrogen upregulates FSH receptor sites. In turn, FSH stimulates granulosa cells to produce estrogens. This synergistic activity of estrogen and FSH allows for follicle growth and development in the ovary. Desensitization The FSHR become desensitized when exposed to FSH for some time. A key reaction of this downregulation is the phosphorylation of the intracellular or cytoplasmic receptor domain by protein kinases. This process uncouples Gs protein from the FSHR. Another way to desensitize is to uncouple the regulatory and catalytic units of the cAMP system. Downregulation Downregulation refers to the decrease in the number of receptor sites. This can be accomplished by metabolizing bound FSHR sites. The bound FSH-receptor complex is brought by lateral migration to a coated pit where such units are concentrated and then stabilized by a framework of clathrins. A pinched-off coated pit is internalized and degraded by lysosomes. Proteins may be metabolized or the receptor can be recycled. Use of long-acting agonists will downregulate the receptor population. Modulators Antibodies to FSHR can interfere with FSHR activity. FSHR abnormalities Some patients with ovarian hyperstimulation syndrome may have mutations in the gene for FSHR making them more sensitive to gonadotropin stimulation.5 Women with 46 XX gonadal dysgenesis experience primary amenorrhea with hypergonadotropic hypogonadism. There are forms of 46 xx gonadal dysgenesis where abnormalities in the FSH-receptor have been reported and are thought to be the cause of the hypogonadism.6 Polymorphism may affect FSH receptor populations and lead to poorer responses in infertile women who receive FSH medication for IVF.7 History Alfred G. Gilman and Martin Rodbell received the 1994 Nobel Prize in Medicine and Physiology for the discovery of the G Protein System. See also Luteinizing hormone/choriogonadotropin receptor References ^ a b c d Simoni, Manuela; Jörg Gromoll Eberhard Nieschlag December 1997. The follicle-stimulating hormone receptor: biochemistry, molecular biology, physiology, and pathophysiology. Endocrine Reviews 18 6: 739-773. doi:10.1210/er.18.6.739. PMID 9408742. Retrieved on 2007-07-01. ^ Piketty, Vincent; Elodie Kara, Florian Guillou, Eric Reiter Pascale Crepieux June 2006. Follicle-stimulating hormone FSH activates extracellular signal-regulated kinase phosphorylation independently of beta-arrestin- and dynamin-mediated FSH receptor internalization. Reproductive Biology and Endocrinology 4 33. doi:10.1186/1477-7827-4-33. PMID 16787538. ^ Asatiani, K.; Gromoll J., Eckardstein S.V., Zitzmann M., Nieschlag E., Simoni M. June 2002. Distribution and function of FSH receptor genetic variants in normal men. Andrologia 34 3: 172-176. doi:10.1046/j.1439-0272.2002.00493.x. PMID 12059813. ^ La Marca, Antonio; Alfredo Carducci Artenisio, Gaspare Stabile, Francesco Rivasi Annibale Volpe December 2005. Evidence for cycle-dependent expression of follicle-stimulating hormone receptor in human endometrium. Gynecological Endocrinology 21 6: 303-306. doi:10.1080/09513590500402756. PMID 16390776. ^ Delbaere, Anne; Guillaume Smits, Anne De Leener, Sabine Costagliola Gilbert Vassart April 2005. Understanding Ovarian Hyperstimulation Syndrome. Endocrine 26 3: 285-290. doi:10.1385/ENDO:26:3:285. PMID 16034183. Retrieved on 2006-07-01. ^ Aittomäki, K.; J.L.D. Lucena, P. Pakarinen, P. Sistonen, J. Tapanainen, J. Gromoll, R. Kaskikari, E.-M. Sankila, H. Lehvaslaiho, A.R. Engel, E. Nieschlag, I. Huhtaniemi A. de la Chapelle September 1995. Mutation in the follicle-stimulating hormone receptor gene causes herary hypergonadotropic ovarian failure. Cell 22 82: 959-68. doi:10.1016/0092-86749590275-9. PMID 7553856. ^ Loutradis, Dimitris; Eleni Patsoula, Vassilis Minas, Giorgos A. Koussidis, Aristeidis Antsaklis, Stylianos Michalas Antonis Makrigiannakis April 2006. FSH receptor gene polymorphisms have a role for different ovarian response to stimulation in patients entering IVF/ICSI-ET programs. Journal of Assisted Reproduction and Genetics 23 4: 177-184. doi:10.1007/s10815-005-9015-z. PMID 16758348. Further reading de la Chapelle A 1993. Disease gene mapping in isolated human populations: the example of Finland.. J. Med. Genet. 30 10: 857-65. PMID 8230163. Amsterdam A, Hanoch T, Dantes A, et al. 2003. Mechanisms of gonadotropin desensitization.. Mol. Cell. Endocrinol. 187 1-2: 69-74. PMID 11988313. Simoni M, Nieschlag E, Gromoll J 2003. Isoforms and single nucleotide polymorphisms of the FSH receptor gene: implications for human reproduction.. Hum. Reprod. Update 8 5: 413-21. PMID 12398222. Delbaere A, Smits G, Olatunbosun O, et al. 2004. New insights into the pathophysiology of ovarian hyperstimulation syndrome. What makes the difference between spontaneous and iatrogenic syndrome?. Hum. Reprod. 19 3: 486-9. doi:10.1093/humrep/deh124. PMID 14998941. Bose CK 2005. Role of nerve growth factor and FSH receptor in epithelial ovarian cancer.. Reprod. Biomed. Online 11 2: 194-7. PMID 16168216. Wunsch A, Sonntag B, Simoni M 2007. Polymorphism of the FSH receptor and ovarian response to FSH.. Ann. Endocrinol. Paris 68 2-3: 160-6. doi:10.1016/j.ando.2007.04.006. PMID 17544358. Kelton CA, Cheng SV, Nugent NP, et al. 1993. The cloning of the human follicle stimulating hormone receptor and its expression in COS-7, CHO, and Y-1 cells.. Mol. Cell. Endocrinol. 89 1-2: 141-51. PMID 1301382. Tilly JL, Aihara T, Nishimori K, et al. 1992. Expression of recombinant human follicle-stimulating hormone receptor: species-specific ligand binding, signal transduction, and identification of multiple ovarian messenger ribonucleic acid transcripts.. Endocrinology 131 2: 799-806. PMID 1322283. Gromoll J, Gudermann T, Nieschlag E 1992. Molecular cloning of a truncated isoform of the human follicle stimulating hormone receptor.. Biochem. Biophys. Res. Commun. 188 3: 1077-83. PMID 1359889. Minegishi T, Nakamura K, Takakura Y, et al. 1991. Cloning and sequencing of human FSH receptor cDNA.. Biochem. Biophys. Res. Commun. 175 3: 1125-30. PMID 1709010. Gromoll J, Ried T, Holtgreve-Grez H, et al. 1994. Localization of the human FSH receptor to chromosome 2 p21 using a genomic probe comprising exon 10.. J. Mol. Endocrinol. 12 3: 265-71. PMID 7916967. Gromoll J, Dankbar B, Gudermann T 1994. Characterization of the 5' flanking region of the human follicle-stimulating hormone receptor gene.. Mol. Cell. Endocrinol. 102 1-2: 93-102. PMID 7926278. Rousseau-Merck MF, Atger M, Loosfelt H, et al. 1993. The chromosomal localization of the human follicle-stimulating hormone receptor gene FSHR on 2p21-p16 is similar to that of the luteinizing hormone receptor gene.. Genomics 15 1: 222-4. doi:10.1006/geno.1993.1041. PMID 8432542. Jiang X, Dreano M, Buckler DR, et al. 1996. Structural predictions for the ligand-binding region of glycoprotein hormone receptors and the nature of hormone-receptor interactions.. Structure 3 12: 1341-53. PMID 8747461. Aittomäki K, Herva R, Stenman UH, et al. 1996. Clinical features of primary ovarian failure caused by a point mutation in the follicle-stimulating hormone receptor gene.. J. Clin. Endocrinol. Metab. 81 10: 3722-6. PMID 8855829. Tapanainen JS, Aittomäki K, Min J, et al. 1997. Men homozygous for an inactivating mutation of the follicle-stimulating hormone FSH receptor gene present variable suppression of spermatogenesis and fertility.. Nat. Genet. 15 2: 205-6. doi:10.1038/ng0297-205. PMID 9020851. Kotlar TJ, Young RH, Albanese C, et al. 1997. A mutation in the follicle-stimulating hormone receptor occurs frequently in human ovarian sex cord tumors.. J. Clin. Endocrinol. Metab. 82 4: 1020-6. PMID 9100567. External links IUPHAR GPCR Database - FSH Receptor GRIS: Glycoprotein-hormone Receptor Information System v d e Transmembrane receptor: G protein-coupled receptors Class A: Rhodopsin like Adrenergic α1 A, B, D, α2 A, B, C, β1, β2, β3 Eicosanoid CysLT 1, 2, LTB4 1, 2, FPRL1, OXE, Prostaglandin DP, EP 1, 2, 3, 4, PGF, Prostacyclin, Thromboxane Neuropeptide B/W 1, 2, FF 1, 2, S, Y 1, 2, 4, 5 Orphan GPR 1, 3, 4, 6, 12, 15, 17, 18, 19, 20, 21, 22, 23, 25, 26, 27, 31, 32, 33, 34, 35, 37, 39, 42, 44, 45, 50, 52, 55, 61, 62, 63, 65, 68, 75, 77, 78, 79, 82, 83, 84, 85, 87, 88, 92, 101, 103, 119, 120, 132, 135, 139, 141, 142, 146, 148, 149, 150, 151, 152, 153, 160, 161, 162, 171, 172, 173, 174, 176, 177, 182 Purinergics Adenosine A1, A2a, A2b, A3, P2Y, 1, 2, 4, 5, 6, 8, 9, 10, 11, 12, 13, 14 Serotonin all but 5-HT3 5-HT1 A, B, D, E, F, 5-HT2 A, B, C, 5-HT 4, 5A, 6, 7 Other Acetylcholine M1, M2, M3, M4, M5 - Adrenomedullin - Anaphylatoxin C3a, C5a - Angiotensin 1, 2 - Apelin - Bile acid - Bombesin BRS3, GRPR, NMBR - Bradykinin B1, B2 - Cannabinoid CB1, CB2 - Chemokine - Cholecystokinin A, B - Dopamine D1, D2, D3, D4, D5 - EBI2 - Endothelin A, B - Estrogen - Formyl peptide 1, L1, L2 - Free fatty acid 1, 2, 3, 4 - FSH - Galanin 1, 2, 3 - Gonadotropin-releasing hormone 1, 2 - Ghrelin - Histamine H1, H2, H3, H4 - Kisspeptin - Luteinizing hormone/choriogonadotropin - Lysophospholipid 1, 2, 3, 4, 5, 6, 7, 8 - MAS 1, 1L, D, E, F, G, X1, X2, X3, X4 - Melanocortin 1, 2, 3, 4, 5 - MCHR 1, 2 - Melatonin 1A, 1B- Motilin - neuromedin B, U 1, 2 - Neurotensin 1, 2 - Opioid Delta, Kappa, Mu, Nociceptin, but not Sigma - Olfactory - Opsin 3, 4, 5, 1LW, 1MW, 1SW, RGR, RRH - Orexin 1, 2 - Oxytocin - Oxoglutarate - PAF - Prokineticin 1, 2 - Prolactin-releasing peptide - Protease-activated 1, 2, 3, 4 - Relaxin 1, 2, 3, 4 - Somatostatin 1, 2, 3, 4, 5 - SREB - Succinate - TAAR 1, 2, 3, 5, 6, 8, 9 - Tachykinin 1, 2, 3 - Thyrotropin - Thyrotropin-releasing hormone - Urotensin-II - Vasopressin 1A, 1B, 2 Class B: Secretin like Brain-specific angiogenesis inhibitor 1, 2, 3 - Cadherin 1, 2, 3 - Calcitonin - CD97 - Corticotropin-releasing hormone 1, 2 - EMR 1, 2, 3 - Glucagon GR, GIPR, GLP1R, GLP2R - Growth hormone releasing hormone - PACAPR1- GPR 56, 64, 97, 98, 110, 111, 112, 113, 114, 115, 116, 123, 124, 125, 126, 128, 133, 143, 144, 157 - Latrophilin 1, 2, 3, ELTD1 - Parathyroid hormone 1, 2 - Secretin - Vasoactive intestinal peptide 1, 2 Class C: Metabotropic glutamate / pheromone Calcium-sensing receptor - GABA B 1, 2 - Glutamate receptor Metabotropic glutamate 1, 2, 3, 4, 5, 6, 7, 8 - GPRC6A - GPR 156, 158, 179 - RAIG 1, 2, 3, 4 - Taste receptors TAS1R 1, 2, 3 TAS2R 1, 3, 4, 5, 8, 9, 10, 12, 13, 14, 16, 38, 39, 40, 41, 43, 44, 45, 46, 47, 48, 49, 50 Frizzled / Smoothened Frizzled 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 - Smoothened v d e Neuropeptide receptors Hypothalamic hormone receptors CRH - FSH - LHRH - TRH - Somatostatin Pituitary hormone receptors Vasopressin 1A, 1B, 2 - Oxytocin - LHCG - Type I cytokine receptor GH, Prolactin - TSH Other hormone receptors Atrial natriuretic factor - Calcitonin - Cholecystokinin A, B - VIP Opioid receptors Delta - Kappa - Mu - Sigma 1, 2 - Nociceptin Other neuropeptide receptors Angiotensin - Bradykinin B1, B2 / Tachykinin TACR1 - Calcitonin gene-related peptide - Galanin - GPCR neuropeptide B/W, FF, S, Y - Neurotensin v d e Sex hormones and related agents primarily G03, also L02, H01C - human endogenous in CAPS Progestogens: receptor Agonist PROGESTERONE, Dienogest, Desogestrel, Drospirenone, Dydrogesterone, Ethisterone, Etonogestrel, Ethynodiol diacetate, Gestodene, Gestonorone, Levonorgestrel, Lynestrenol, Medroxyprogesterone, Megestrol, Norelgestromin, Norethisterone, Norethynodrel, Norgestimate, Norgestrel, Norgestrienone, Tibolone SPRM Asoprisnil, CDB-4124 Antiprogestogen Mifepristone Androgens: receptor Agonist TESTOSTERONE, Androstanolone, Fluoxymesterone, Mesterolone, Methyltestosterone, see also anabolic steroids Antiandrogen Bicalutamide, Cyproterone, Dienogest, Flutamide, Nilutamide, Spironolactone Estrogens: receptor Agonist ESTRADIOL, ESTRIOL, ESTRONE, Chlorotrianisene, Dienestrol, Diethylstilbestrol, Ethinylestradiol, Fosfestrol, Mestranol, Polyestradiol phosphate SERM Afimoxifene, Arzoxifene, Bazedoxifene, Clomifene, Fulvestrant, Lasofoxifene, Raloxifene, Tamoxifen, Toremifene AI Aminoglutethimide, Anastrozole, Atamestane, Exemestane, Fadrozole, Formestane, Letrozole, Vorozole Antiestrogen Mepitiostane Gonadotropins: FSHR/LHCGR ovulation stim. Clomifene, Urofollitropin Antigonadotropin Danazol, Gestrinone GnRH: receptor Agonist Buserelin, Goserelin, Histrelin, Leuprorelin, Nafarelin, Triptorelin Antagonist Abarelix, Cetrorelix, Ganirelix Retrieved from http://en..org/wiki/FSH-receptor Categories: Genes on chromosome 2 | Human proteins | Cell signaling | Signal transduction | G protein coupled receptors Views Article Discussion this page History Personal tools Log in / create account Navigation Main page Contents Featured content Current events Random article Search Go Search Interaction Community portal Recent changes Contact Donate to Help Toolbox What links here Related changes Upload file Special pages Printable version Permanent link Cite this page This page was last modified on 8 July 2008, at 02:42
39 Reasons to Drink Acai Juice Every Day
What is MonaVie - Watch the 8-minute video
Discovering MonaVie Video
The Power of You Video
Effects of MonaVie Active on Antioxidant Capacity in Humans
Log into your Wholesale MonaVie Account
So many of us do not eat a balanced diet, get enough sleep, have too much stress, or are impacted with toxins and pollutants. Drinking 2 ounces of MonaVie twice a day will help your body detoxify as well as build your immune system. Its the smartest thing you can do for yourself, so start today. Buying MonaVie through our company guarantees you support 7 days a week and, if you would like to share MonaVie with your family and friends we will guide you from start to finish.
1. Click on Enroll Now (30 - 55% off retail price)
2. Pay $39 for your Wholesale ID number.
3. NO minimum order required.
4. MonaVie is delivered to your door in 3 to 5 days.