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Lecture 3

Endocrine Lecture 3- Receptors & Signalling

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Michelle French

Endocrine L3 Nov 16 11testosteroneso ReceptorsSignallingandrogens preferredHow do hormones signalWhat are the two main types of receptorsHormone have to bind to receptor to workIntracellular receptors bind lipid solubleChanges conformationactivity of hormonesreceptorCytosolicnuclear Alters activity of intracellular signaling Complex directly alter gene transcriptn pathwaysgenomic effects change in synthesis of target prots andor Plasma membrane receptorsmodification of existing target protsIntermediary pathwayG proteincoupled receptorsmost common typeReceptorenzyme receptorsIntracellular receptorsReceptor at cell membrane cytoplasm or nucleusHydrophilic prots peptides catecholaminesonly interact w receptors on surfaceHydrophobic steroid thyroid hormonesfuse w plasma membrane thru to cytoplasm all 3 waysWhat characteristics do receptors shareLarge protsFamiliescan have several receptors that bind to same hormoneCan be multiple receptors for 1 ligand or 1 ligand for a receptor ex Adrenergic for Where the receptor is depends on kind of receptoradrenalinnoradrenalinEx Bind to cytoplasmic receptorreceptor shape Variablein target cell 500100000changeunmask nuclear localization signaldepending on biology of organismdirects complex to nucleuscomplex binds to Activatedinhibitedspecific DNA seqs hormone response Located in cell membrane cytoplasm nucleuselementsEx Hormone diffuses into nucleusbinds to Properties of receptorsnuclear receptorshape changesallows for High affinitybinds stronger to certain hormonesinteraction w DNADNAhormonereceptor Saturableonly bind certain amt of hormonecomplex sometimes recruits coactivators or Specific3D shape of receptorhormone corepressors to affect transcriptnchange in somewhat but not completelytranscriptn often increase of any genes that Reversiblenoncovalent binding so hormone contain the particular hormone response element can diffuse away mRNA leaves nucleustranslatn on ribosomes in cytoplasmcertain prots madeCellular receptors are saturableOver certain amt no How hormonereceptor binding to DNA more hormone bound inside cellreceptor saturated only have max effect of hormoneReceptorhormone binding is reversiblespecificNot completely specificAdd nonlabelled testosteronecompete w labelledEstrogen fits nicely into certain pocket interacts w binds to receptorsestrogen response elementspecific DNA seq w competes away certain shape able to bind to receptor complexlabelled hormoneReceptor complex acts like transciptn factor or Need higher gene regulatory protcan recruit coactivators concentratn for histone acetylases chromatin remodelling estrogen to knock off
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