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The main pharmacodynamic characteristics of the SERMs that are currently available reflect their antineoplastic activity in estrogen-dependent breast cancer (tamoxifen and toremifene) and the beneficial effects on bone remodeling, bone mineral density, and reduction of osteoporotic fractures in postmenopausal women observed with raloxifene. However, one major consequence of the Women's Health Initiative findings has been an increased interest in the full therapeutic potential of SERMs - still...

Cooh 919

ERs contain two structures called zinc fingers, typical of proteins that interact with DNA. One zinc atom forms four links of coordination with four cysteine residues of the protein structure, which occupy nearby positions, thus leaving aloop of some 15to22 aminoacids. The zinc fingers of the receptor are capable ofinteracting with specific sequences of DNA, the hormone response elements, with which they establish hydrogen bridges and form stable structures Fig....

Mechanism of Action in the Endometrium

As has been widely commented in previous chapters, the agonist antagonist profile of a given SERM is determined by the type of compound and the particular target tissue. Members of the different SERM families bind to the ligand-binding domain (LBD) of the ER, whose particular crystal structure has been revealed for estradiol and for raloxifene (Brzozowski et al. 1997). Once inserted into the binding cavity, estradiol makes direct hydrogen bonds bewteen its A-ring and the carboxylate of Glu 353,...

Contents

1 Molecular Mechanisms of Estrogen Action in Target Tissues B. Nicol s D az Chico, Domingo Navarro Bosch, Juan C. D az Chico, Eduardo Escrich Escriche 1.2 General Aspects 1.2.1 The Discovery of Hormone Receptors for Steroid Hormones 4 1.2.2 Nuclear Hormone 1.3.1 Primary Structure of Estrogen 1.3.2 Activity Domains in the Molecules of Estrogen Receptors 8 1.3.3 Genetic Encoding of Estrogen 1.3.4 Native 1.3.5 Estrogen Transforms the Native 1.4 Hormone-Receptor 1.4.1 Ligand Binding 1.4.2 Structure...