Hormoni – razlika između verzija

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== Receptori ==
[[File:Steroid and Lipid Hormones.svg|thumb|400px|Levi dijagram prikazuje [[Steroidni hormon|steroidni]] ([[lipid]]ni) hormon:<ref>{{cite journal| author= Funder JW, Krozowski Z, Myles K, Sato A, Sheppard KE, Young M |title= Mineralocorticoid receptors, salt, and hypertension |year = 1997|url= | journal= Recent Prog Horm Res | volume= 52 |pages = 247–260 |pmid= 9238855 }}</ref><ref name=gup>{{cite journal| author= Gupta BBP, Lalchhandama K |title= Molecular mechanisms of glucocorticoid action |year = 2002|url=http://www.currentscience.ac.in/Downloads/article_id_083_09_1103_1111_0.pdf | journal= Current Science | volume= 83 | issue= 9 |pages = 1103–1111 |pmid= |pmc= |doi= }}</ref><ref>{{cite journal| author= Frye CA |title= Steroids, reproductive endocrine function, and affect. A review |year = 2009|url= | journal= Minerva Ginecol | volume= 61 | issue= 6 |pages = 541–562 |pmid= 19942840 }}</ref> (1) ulazak u ćeliju i (2) vezivanje za protein receptora u jedru, čime se uzrokuje (3) sinteza iRNK, što je prvi korak u [[Sinteza proteina|proteinskoj sintezi]]. Na desnoj strani su prikazani proteinski hormoni: (1) vezivanje za receptore čime se (2) započinje prenos signala. Putevi transdukcije se završavaju (3) sa aktivacijom transkripcionih faktora u jedru, i početkom proteinske sinteze. U oba dijagrama, „a“ označava hormon, „b“ ćelijsku membranu, „c“ citoplazmu, i „d“ jedro.]]
[[File:Steroid and Lipid Hormones.svg|thumb|400px|The left diagram shows a steroid (lipid) hormone (1) entering a cell and (2) binding to a receptor protein in the nucleus, causing (3) mRNA synthesis which is the first step of protein synthesis. The right side shows protein hormones (1) binding with receptors which (2) begins a transduction pathway. The transduction pathway ends (3) with transcription factors being activated in the nucleus, and protein synthesis beginning. In both diagrams, a is the hormone, b is the cell membrane, c is the cytoplasm, and d is the nucleus.]]
 
Većina hormona inicira ćelijske response inicijalnim vezivanjem bilo za [[membranski protein|membranske proteine]] ili [[Intracelularni| intraćelijske]] [[receptor (biohemija)|receptore]]. Ćelija može da ima nekoliko različitih tipova receptora koji prepoznaju isti hormon, a aktiviraju različite puteve [[Prenos signala (biologija)|prenosa signala]], ili može da ima nekoliko različitih receptora koji prepoznaju različite hormone, a aktiviraju isti biohemijski put.<ref>{{Cite book |ref= harv|last= Loewenstein|first= Werner R. |authorlink= |editor= |others= |title=The Touchstone of Life: Molecular Information, Cell Communication, and the Foundations of Life |edition= |language= |publisher=Oxford University Press |location=Oxford [Oxfordshire] |year=2000 |origyear= }}</ref><ref>{{Cite book |ref= harv|last= Kramer|first= IJsbrand M.; Bastien D. Gomperts |authorlink= |editor= |others= |title=Signal Transduction, Second Edition |edition= |language= |publisher=Academic Press |location=Boston |year=2009 |origyear= }}</ref><ref>{{Cite book |ref= harv|author=Julia Cooper; Gerhard Krauss; Nancy Schonbrunner |authorlink= |editor= |others= |title=Biochemistry of Signal Transduction and Regulation, 2nd Edition |edition= |language= |publisher=Wiley-VCH |location=Weinheim |year=2001 |origyear= }}</ref>
Most hormones initiate a cellular response by initially binding to either [[membrane protein|cell membrane associated]] or [[intracellular]] [[receptor (biochemistry)|receptor]]s. A cell may have several different receptor types that recognize the same hormone but activate different [[signal transduction]] pathways, or a cell may have several different receptors that recognize different hormones and activate the same biochemical pathway.
 
Receptori većine [[peptidni hormon|peptidnih]], kao i mnogih [[eikosanoid]]nih hormona, su smešteni u [[ćelijska membrana|ćelijskoj membrani]] na površini ćelije i većina tih receptora pripada klasi [[G protein spregnuti receptor|G protein spregnutih receptora]] (GPCR),<ref name=trz>{{Cite pmid|22300046}}</ref><ref name="pmid12869759">{{cite journal | author = King N, Hittinger CT, Carroll SB | title = Evolution of key cell signaling and adhesion protein families predates animal origins | journal = Science | volume = 301 | issue = 5631 | pages = 361–3 | year = 2003 | pmid = 12869759 | doi = 10.1126/science.1083853 }}</ref><ref>{{cite journal | author= Filmore D | pages=24–28 | title=It's a GPCR world | journal = Modern Drug Discovery | volume=2004 | year=2004 | issue=November | publisher=American Chemical Society | url = http://pubs.acs.org/subscribe/journals/mdd/v07/i11/html/1104feature_filmore.html }}</ref><ref name="pmid17139284">{{cite journal | author = Overington JP, Al-Lazikani B, Hopkins AL | title = How many drug targets are there? | journal = Nat Rev Drug Discov | volume = 5 | issue = 12 | pages = 993–6 |date=December 2006 | pmid = 17139284 | doi = 10.1038/nrd2199 }}</ref> proteina sa sedam [[Transmembranski protein|transmembranskih]] [[alfa heliks]]a.<ref name="Goodman2008">{{cite book|author=Steven R. Goodman|title=Medical cell biology|url=http://books.google.com/books?id=WO6EVUgWw7AC&pg=PA37|accessdate=24 November 2010|year=2008|publisher=Academic Press|isbn=978-0-12-370458-0|pages=37–}}</ref> Interakcija hormona i receptora tipično inicira kaskadu sekundarnih efekata u ćelijskoj [[citoplazma|citoplazimi]], što obično obuhvata [[fosforilacija|fosforilaciju]] ili defosforilaciju raznih drugih citoplazmatičnih proteina, promene propustljivosti [[jonski kanal|jonskih kanala]], ili povećane koncentracije intracelularnih molekula koji mogu da deluju kao [[Sistem sekundarnih glasnika|sekundarni glasnici]]<ref name="Kimball">{{cite web|author= Kimball, J|title=Second messengers | url=http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/S/Second_messengers.html}}</ref><ref>{{MeshName |Second+Messenger+Systems}}</ref> (e.g., [[ciklični AMP]]). Neki od [[peptidni hormon|proteinskih hormona]]<ref>[http://books.google.com/books?id=hrp1AAAACAAJ ''Peptide Hormone Secretion/Peptide Hormone Action: A Practical Approach,''] K. Siddle, J. C. Hutton, Oxford University Press, 1991, ISBN 0-19-963073-9.</ref><ref>[http://books.google.com/books?id=QmNrJgAACAAJ&dq=peptide+hormone ''Peptide Hormone Secretion: A Practical Approach,''] J. C. Hutton, Hull University Press, 1991, ISBN 0-19-963068-2.</ref> takođe formiraju interakcije sa [[Intracelularni|intracelularnim]] receptorima<ref name="isbn0-7167-7601-4">{{cite book |author=Matsudaira, Paul T.; Lodish, Harvey F.; Arnold Berk; Kaiser, Chris; Monty Krieger; Matthew P Scott; Anthony Bretscher; Hidde Ploegh |authorlink= |editor= |others= |title=Molecular cell biology |edition= |language= |publisher=W.H. Freeman |location=San Francisco |year=2008 |origyear= |pages= |quote= |isbn=0-7167-7601-4 |oclc= |doi= |url= |accessdate=}}</ref> lociranim u citoplazmi ili [[ćelijsko jedro|jedru]] putem [[intrakrinog]] mehanizma.<ref>{{cite journal | last1 = Re | first1 = RN | date = Apr 2003 | title = The intracrine hypothesis and intracellular peptide hormone action | url = | journal = BioEssays | volume = 25 | issue = 4| pages = 401–9 | doi = 10.1002/bies.10248 | pmid = 12655647 }}</ref><ref>{{cite journal | last1 = Re | first1 = RN | date = Jan 2002 | title = The origins of intracrine hormone action | url = | journal = Am J Med Sci. | volume = 323 | issue = 1| pages = 43–8 | pmid = 11814142 | doi=10.1097/00000441-200201000-00008}}</ref><ref>Kumar R, Singh VP, Baker KM. "The intracellular renin-angiotensin system: a new paradigm. ''Trends Endocrinol Metab.'' 2007 May 15. {{DOI|10.1016/j.tem.2007.05.001}} PMID 17509892.</ref><ref>{{cite journal | last1 = Fiaschi-Taesch | first1 = NM | last2 = Stewart | first2 = AF | date = Feb 2003 | title = Minireview: parathyroid hormone-related protein as an intracrine factor--trafficking mechanisms and functional consequences | url = | journal = Endocrinology | volume = 144 | issue = 2| pages = 407–11 | doi = 10.1210/en.2002-220818 | pmid = 12538599 }}</ref>
Receptors for most [[peptide hormone|peptide]] as well as many [[eicosanoid]] hormones are embedded in the [[plasma membrane]] at the surface of the cell and the majority of these receptors belong to the [[G protein-coupled receptor]] (GPCR) class of seven [[alpha helix]] [[transmembrane]] proteins. The interaction of hormone and receptor typically triggers a cascade of secondary effects within the [[cytoplasm]] of the cell, often involving [[phosphorylation]] or dephosphorylation of various other cytoplasmic proteins, changes in [[ion channel]] permeability, or increased concentrations of intracellular molecules that may act as [[second messenger|secondary messengers]] (e.g., [[cyclic AMP]]). Some [[protein hormone]]s also interact with [[intracellular]] receptors located in the [[cytoplasm]] or [[Cell nucleus|nucleus]] by an [[intracrine]] mechanism.
 
U slučaju [[steroidni hormon|steroidnih]] ili [[tiroidni hormon|tiroidnih]] hormona, [[steroidni hormonski receptor|receptori]] su locirani [[Intracelularni|unutar ćelije]] u citoplazmi ciljne ćelije. Ti receptori pripadaju familiji [[nuklearni receptor|nuklearnih receptora]]
For [[steroid hormone|steroid]] or [[thyroid hormone|thyroid]] hormones, their [[steroid hormone receptor|receptors]] are located [[intracellular|inside the cell]] within the [[cytoplasm]] of the target cell. These receptors belong to the [[nuclear receptor]] family of ligand-activated [[transcription factor]]s. To bind their receptors, these hormones must first cross the cell membrane. They can do so because they are lipid-soluble. The combined hormone-receptor [[protein complex|complex]] then moves across the nuclear membrane into the nucleus of the cell, where it binds to specific [[DNA sequences]], regulating the expression of certain [[genes]], and thereby increasing the levels of the proteins encoded by these genes.<ref name=beato>{{cite journal | author =Beato M, Chavez S and Truss M | title = Transcriptional regulation by steroid hormones | journal = Steroids | year=1996 | volume=61 | issue=4 | pages=240–251 | pmid = 8733009 | doi = 10.1016/0039-128X(96)00030-X}}</ref> However, it has been shown that not all steroid receptors are located inside the cell. Some are associated with the [[plasma membrane]].<ref name=hammes>{{cite journal | author =Hammes SR | title = The further redefining of steroid-mediated signaling | journal = Proc Natl Acad Sci USA | year=2003 | volume=100 | issue=5 | pages=21680–2170 | pmid = 12606724 | doi = 10.1073/pnas.0530224100 | pmc =151311}}</ref>
<ref name = "Evans_1988">{{vcite2 journal | vauthors = Evans RM | title = The steroid and thyroid hormone receptor superfamily | journal = Science | volume = 240 | issue = 4854 | pages = 889–95 | year = 1988 | doi = 10.1126/science.3283939 | pmid = 3283939}}</ref><ref name = "Olefsky_2001">{{vcite2 journal | vauthors = Olefsky JM | title = Nuclear receptor minireview series | journal = J. Biol. Chem. | volume = 276 | issue = 40 | pages = 36863–4 | year = 2001 | pmid = 11459855 | doi = 10.1074/jbc.R100047200 }}</ref> koji su ligandom aktivirani [[transkripcioni faktor]]i.
<ref name = "Wärnmark_2003">{{vcite2 journal | vauthors = Wärnmark A, Treuter E, Wright AP, Gustafsson J-Å | title = Activation functions 1 and 2 of nuclear receptors: molecular strategies for transcriptional activation | journal = Mol. Endocrinol. | volume = 17 | issue = 10 | pages = 1901–9 | year = 2003 | pmid = 12893880 | doi = 10.1210/me.2002-0384 }}</ref><ref name="Weatherman_1999">{{cite journal | author = Weatherman RV, Fletterick RJ, Scanlan TS | title = Nuclear-receptor ligands and ligand-binding domains | journal = Annu. Rev. Biochem. | volume = 68 | issue = | pages = 559–81 | year = 1999 | pmid = 10872460 | doi = 10.1146/annurev.biochem.68.1.559 }}</ref> Da bi se vezali za svoje receptore, ti hormoni prvo moraju da prođu kroz ćelijsku membranu. Do toga može da dođe zato što su oni rastvorni u lipidima. Kombinovani [[proteinski kompleks|kompleks]] hormona i receptora se zatim premešta kroz membranu u ćelijsko jedro, gde se vezuje za specifične [[Sekvenca nukleinskih kiselina|DNK sekvence]].<ref>{{cite journal | last = Samarsky | first = DA |author2=Fournier MJ |author3=Singer RH |author4=Bertrand E | year = 1998 | title = The snoRNA box C/D motif directs nucleolar targeting and also couples snoRNA synthesis and localization | journal = EMBO | volume = 17 | pages = 3747–3757 | pmid = 9649444 | doi = 10.1093/emboj/17.13.3747 | issue = 13 | pmc = 1170710 }}</ref><ref>{{cite doi|10.1101/gad.11.7.941}}</ref> Time se reguliše izražavanje pojedinih [[gen]]a, i stoga povećavaju nivoi proteina kodiranih tim genima.<ref name=beato>{{cite journal | author =Beato M, Chavez S and Truss M | title = Transcriptional regulation by steroid hormones | journal = Steroids | year=1996 | volume=61 | issue=4 | pages=240–251 | pmid = 8733009 | doi = 10.1016/0039-128X(96)00030-X}}</ref> Pokazano je da svi steroidni receptori nisu locirani unutar ćelije. Neki su vezani za ćelijsku membranu.<ref name=hammes>{{cite journal | author =Hammes SR | title = The further redefining of steroid-mediated signaling | journal = Proc Natl Acad Sci USA | year=2003 | volume=100 | issue=5 | pages=21680–2170 | pmid = 12606724 | doi = 10.1073/pnas.0530224100 | pmc =151311}}</ref>
 
== Hormonski efekti ==