Table of ContentsSELECTIVE ESTROGEN RECEPTOR MODULATORS (SERMs): IMPLICATIONS FOR CLINICAL CNS ACTIONS SERMsî INCLUDE ALL ESTROGEN RECEPTOR (ER) LIGANDS, INCLUDING RALOXIFENE (RLX), TAMOXIFEN (TMX), GENISTEIN (GEN) AND 17_ -ESTRADIOL (E2). THESE ARE PROTOTYPICAL COMPOUNDS THAT ARE CLINICALLY AVAILABLE. BIOLOGICAL EFFECTS OF EACH SERM WILL DIFFER: EACH HAS CHARACTERISTIC BINDING AFFINITY AND ACTIONS VIA THE TWO ER SUBTYPES (ER_ AND ER_) AND ALSO MAY AFFECT CO-TRANSACTIVATING FACTORS DIFFERENTIALLY. THE BRAIN HAS OVERLAPPING FUNCTIONAL- AND ER SUBTYPE DOMAINS. THE FORMER IS DUE TO INTRA- AND INTERNUCLEAR NEURONAL CONNECTIONS. ER SUBTYPE OVERLAP IMPLIES POSSIBLE HOMO- AND HETERODIMERIZATION. PPT Slide PPT Slide PPT Slide PPT Slide CLINICAL CNS EFFECTS OF SERMs HAVE BEEN SOUGHT ON THE BASIS OF THE EFFECTS OF ESTROGEN DEFICIENCY AND REPLACEMENT, AND ANIMAL STUDIES. BUT, PROOF OF CLINICAL EFFICACY IS LIMITED AND UNDISCOVERED ACTIONS MAY EXIST. GENERALIZATIONS MUST BE AVOIDED. CLINICAL EFFECTS OF SERMs PRESENTLY, NOT ENOUGH IS KNOWN OF CLINICAL CNS ACTIONS OF SERMs TO PROPERLY COMPARE E2 EFFECTS WITH RLX, TMX OR GEN. NOTHING IS KNOWN OF CLINICAL EFFECTS OF COMBINATIONS. TO EXPLORE THESE ISSUES WE HAVE USED IN VITRO ASSAYS. NEUROTROPHIC ASSAYS TEST THE ABILITY OF SERMS TO INDUCE GROWTH OF NEURAL PROCESSES. Effect of Estrogenic Compounds on Organotypic Cultures PPT Slide PPT Slide PPT Slide Effect of SERMs on Neurite Outgrowth Antagonism of Estrogenic-Induced Neurite Outgrowth in PC12 Cells Effect of Raloxifene and Genistein on Estrogen Induced Neurite Outgrowth NEUROPROTECTION ASSAYS TEST THE EFFECT OF SERMS ON THE GROWTH RATE (CELL DIVISION MINUS CELL DEATH). Expression of Estrogen Receptors Alpha and Beta in Neuronal cell lines Expression of Estrogen receptors on Neuronal-Like cells PPT Slide PPT Slide Estrogen Induced Apoptosis SUMMARY SUMMARY SUMMARY CONCLUSIONS |
Author: Dr. Gil Mor
Email: gil.mor@yale.edu Home Page: http://info.med.yale.edu/obgyn/reproimmuno/ |