Selective Estrogen Receptor Modulators (SERMs) are a class of compounds that act on the estrogen receptor.[1] A characteristic that distinguishes these substances from pure receptor agonists and antagonists is that their action is different in various tissues, thereby granting the possibility to selectively inhibit or stimulate estrogen-like action in various tissues. Phytoserms are SERMs from a botanical source.
Contents |
SERMs are used dependent on their pattern of action in various tissues:
| Name | Uses | Effects/location |
|---|---|---|
| clomifene | used in anovulation | antagonist at hypothalamus |
| femarelle | managing menopause symptoms, osteoporosis | agonist at brain and bone |
| ormeloxifene | contraception | agonist at bone; antagonist at breast and uterus |
| raloxifene | osteoporosis, breast cancer | agonist at bone; antagonist at breast and uterus |
| tamoxifen | breast cancer | agonist at bone and uterus, antagonist at breast |
| toremifene | breast cancer | |
| lasofoxifene | osteoporosis, breast cancer, vaginal atrophy | agonist at the bone, antagonist at breast and uterus |
Other members include afimoxifene, arzoxifene, and bazedoxifene.
Some SERMs may be good replacements for hormone replacement therapy (HRT), which had been commonly used to treat menopause symptoms until the publication of wide scale studies showing that HRT slightly increases the risk of breast cancer [2] and thrombosis.[3] Some of the above agents still have significant side-effects that contraindicate widespread use.
Estrogenic compounds span a spectrum of activity ranging from:
The mechanism of mixed agonism/antagonism may differ depending on the chemical structure of the SERM, but, for at least for some SERMs, it appears to be related to (1) the ratio of co-activator to co-repressor proteins in different cell types and (2) the conformation of the estrogen receptor induced by drug binding, which in turn determines how strongly the drug/receptor complex recruits co-activators (resulting in an agonist response) relative to co-repressors (resulting in antagonism). For example, the prototypical SERM tamoxifen acts as an antagonist in breast and conversely an agonist in uterus. The concentration of steroid receptor co-activator 1 (SRC-1; NCOA1) is higher in uterus than in breast, therefore SERMs such as tamoxifen are more agonistic in uterus than in breast. In contrast, raloxifene behaves as an antagonist in both tissues. It appears that raloxifene more strongly recruits co-repressor proteins and consequently is still an antagonist in the uterus despite the higher concentration of co-activators relative to co-repressors.[4][5]
The actions of SERMs on various tissues:
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||