Edited by:Mohammad  Hezarkhani  MD,Urologist

Board-Certified of Urology,Tehran  University ,The Member  of  Iranian  Urological  Association

Madaen Hospital  Tehran Iran

Mohammad.hezarkhani@yahoo.com

www.facebook.com/mohammad.hezarkhani.1

June,20 , 2013

Selective estrogen receptor modulators (SERMs) are a class of compounds that act on the estrogen receptor. 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.

Estrogenic compounds span a spectrum of activity ranging from:

  • full agonists (agonistic in all tissues) such as the natural endogenous hormone estrogen
  • mixed agonists/antagonistics (agonistic in some tissues while antagonist in others) such as tamoxifen (a SERM)
  • pure antagonists (antagonistic in all tissues) such as fulvestrant (ICI-182780).

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.

The actions of SERMs on various tissues:

  • Bone turnover and postmenopausal osteoporosis respond favorably to most SERMs, although premenopausal women may experience bone loss with some SERMs including tamoxifen.
  • Breast - all SERMs decrease breast cancer risk, and tamoxifen is mainly used for its ability to inhibit growth in estrogen receptor-positive breast cancer.
  • Cholesterol and triglycerides - levels respond favorably to SERMs.
  • Deep venous thrombosis - the risk may be elevated in at least some SERMs.
  • Hot flashes are increased by some SERMs.
  • Pituitary gland - clomifene blocks estrogen action, leading to an increase of follicle-stimulating hormone and luteinizing hormone.
  • Uterus - tamoxifen may increase endometrial carcinoma risk, but raloxifene and femarelle do not. Data on toremifene and clomifene is insufficient.
  • There is ample evidence in literature that suggests the role of estrogens in BPH development and management through the different tissue and cell-specific receptors. This article reviews beneficial actions of selective estrogen receptor modulator (SERM) and ERβ-selective ligands, which have been demonstrated through in vitro studies using human prostate cell lines and in vivo animal studies. SERMs have anti-proliferative, anti-inflammatory and pro-apoptotic mechanisms in BPH, and also act by inhibiting various growth factors, and thus represent a unique and novel approach in BPH management directed at estrogen receptors or estrogen metabolism.

References:

1- Prostate Cancer and Prostatic Diseases , (18 June 2013) | doi:10.1038/pcan.2013.17

Selective estrogen receptor modulators for BPH: new factors on the ground/M Garg, D Dalela, D Dalela, A Goel, M Kumar, G Gupta and S N Sankhwar

2-Wikipedia.The Free Encyclopedia, Selective estrogen-receptor modulator/27.Feb.2013