SERMS Flashcards
excessive exposure to osteorgen is associated
with risk of breast cancer
early menarche
late menopause
nulliparty
ERa
always an activator
more important in breast and uterus
ERb
sometimes a repressor and more important in CVS
both ERa and ERb are important for
for bone health and CVS protection
nucelar receptos bind DNA via
response elements
NR associated co-factors
do the transcriptional modulating
lots of cofactors
have tissues restricted expression patterns, results in increased complexity and tissue specific activity
ERb may
modulate Era function in breast and uterus
Era appears oncogenic while ERb has tumour suppressor functions
oestrogens and bone health
Era and ERb are expressed in bone and BM cells
increase in estradiol at puberty triggers long bone growth
estradiol maintains bone mineral density in adults
protective effects of estradiol
maintains bone miner density in adults
inhibits osteoclasts and promoting osteoblasts and osteocyte survival
SERMS
compounds that exhibit tissue-specific ER agonist or antagonist activity
non steroidal
all SERMs are nonsterodal except
fulvestrant
effects off SERMS
varying effects in different tissues but often
- anti-oostrogenic effect on breast epithelium
- oestrogenic effect on bone
SERMS mechanism of action
often bigger
prevent helix 12 from closing
co activators can’t bind - pure antagonist
net agonist/antagonist activity of ER ligands
depends on ligand-induced ER conformational changes, ER isoform (a or B) and recruited co-factors
SERMS act as
oestrogens on some tissues but anti oestrogens on others
