Nuclear-receptors(核受体))-豆柴文库

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INTRACELLULARRECEPTORSTheintracellular(nuclear)receptorsuperfamily
Steroidhormones,thyroidhormones,retinoidsandvitaminDRegulationoftranscriptionactivityIntracellularsignalmolecules
small,lipid-solublemoleculessuchassteroidhormones,retinoids,thyroidhormones,VitaminD.(madefromcholesterol)
Thesemoleculesdiffusethroughplasmaandnuclearmembranesandinteractdirectlywiththetranscriptionfactorstheycontrol.67SteroidHormonesBIOSYNTHESISOFSTEROIDSEndocrinedisruptionToxicantsinteractwithhormonalsystematdifferentlevelsbiosynthesisandreleaseofhormonesMechanismsofsteroidhormonessignallingdisruptionEndocrinedisruptersintheenvironment?ESTROGENRECEPTOR–ERthemoststudiedtargetofEDCsEstrogens:


playakeyroleinfemalehormoneregulationandsignalling
areresponsibleformetabolic,behaviouralandmorphologicchangesoccurringduringstagesofreproduction
areinvolvedinthegrowth,developmentandhomeostasisofanumberoftissues
controltheboneformation,regulationofhomeostasis,cardiovascularsystemandbehaviour
regulateproduction,transportandconcentrationoftesticularliquidandanabolicactivityofandrogensinmales

Synthesisinovaries

DISRUPTION->investigatedinaquaticbiota&laboratoryorganisms(seenotesonEDCs)ESTROGENRECEPTORS-ER-&ER-:

subtype:ER-(inbreast,ovary,brain,liver,boneandcardiovascularsystem,adrenals,testisandurogenitaltract)
ER-(inkidneys,prostateandgastrointestinaltract)

	(ER-infish)
Naturalproducts
genistein
naringenin
coumestrol
zearalenoneExoestrogens-RelativePotenciestobindtoERa(REPs)ToxicityassessmentnumberofinvivoandinvitromethodsInvitroassaysER-mediatedeffects
luciferasereporterassayInvivoassaysKidd,K.A.etal.2007.Collapseofafishpopulationfollowingexposuretoasyntheticestrogen.ProceedingsoftheNationalAcademyofSciences104(21):8897-8901ANDROGENRECEPTOR(AR)effectsknownbutlessexploredthanERAndrogensAndrogensMechanismsofandrogensignallingdisruptionMechanismsofandrogensignallingdisruptionEffectsofmaleexposuretoantiandrogensAntiandrogeniccompoundAR-binding-potencies(Ref:DHTEC50~0.1uM)(Anti)androgenicityass