In females, estrogens play a key role in reproduction and have beneficial 
effects on the skeletal, cardiovascular, and central nervous systems. Most 
estrogenic responses are mediated by estrogen receptors (ERs), either ER alpha 
or ER beta, which are members of the nuclear receptor superfamily of 
ligand-dependent transcription factors. Selective estrogen receptor modulators 
(SERMs) are ER ligands that in some tissues act like estrogens, but block 
estrogen action in others. Thus, SERMs may exhibit an agonistic or antagonistic 
biocharacter depending on the context in which their activity is examined. For 
example, the SERMs tamoxifen and raloxifene both exhibit ER antagonist activity 
in breast and agonist activity in bone, but only tamoxifen manifests agonist 
activity in the uterus. Numerous studies have examined the molecular basis for 
SERM selectivity. Collectively they indicate that different ER ligands induce 
distinct structural changes in the receptor that influence its ability to 
interact with other proteins (e.g., coactivators or corepressors) critical for 
the regulation of target gene transcription. The relative expression of 
coactivators and corepressors, and the nature of the ER and of its target gene 
promoter affect SERM biocharacter. Taken together, SERM selectivity reflects the 
diversity of ER forms and coregulators, cell type differences in their 
expression, and the diversity of ER target genes. This model provides a basis 
for understanding the molecular mechanisms of SERM action, and should help 
identify new SERMs with enhanced tissue or target gene selectivity.