World Library  
Flag as Inappropriate
Email this Article

Selective estrogen-receptor modulator

Article Id: WHEBN0001088710
Reproduction Date:

Title: Selective estrogen-receptor modulator  
Author: World Heritage Encyclopedia
Language: English
Subject: Selective estrogen receptor modulators, Hormone antagonists, Corticotropin-releasing hormone antagonist, Prostaglandin antagonist, Birth control methods
Collection: Selective Estrogen Receptor Modulators
Publisher: World Heritage Encyclopedia
Publication
Date:
 

Selective estrogen-receptor modulator

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

  • Members and uses 1
  • Mechanism of action 2
  • Actions 3
  • See also 4
  • References 5
  • External links 6

Members and uses

Nolvadex (tamoxifen) 20-milligram tablets (UK)

SERMs are used dependent on their pattern of action in various tissues:

Name Uses Effects/location
clomifene ovulation induction in anovulation antagonist at hypothalamus
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
ospemifene vaginal atrophy, dyspareunia 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.

Mechanism of action

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.[4][5]

Actions

The actions of SERMs on various tissues:

See also

References

  1. ^ Riggs BL, Hartmann LC (2003). "Selective estrogen-receptor modulators -- mechanisms of action and application to clinical practice". N Engl J Med 348 (7): 618–29.  
  2. ^ Reeves GK, Beral V, Green J, Gathani T, Bull D (November 2006). "Hormonal therapy for menopause and breast-cancer risk by histological type: a cohort study and meta-analysis". Lancet Oncol. 7 (11): 910–8.  
  3. ^ Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, Jackson RD, Beresford SA, Howard BV, Johnson KC, Kotchen JM, Ockene J; Writing Group for the Women's Health Initiative Investigators (July 2002). "Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial". JAMA 288 (3): 321–33.  
  4. ^ Shang Y, Brown M (2002). "Molecular determinants for the tissue specificity of SERMs". Science 295 (5564): 2465–8.  
  5. ^ Smith CL, O'Malley BW (2004). "Coregulator function: a key to understanding tissue specificity of selective receptor modulators". Endocr Rev 25 (1): 45–71.  

External links

  • AACR Cancer Concepts Factsheet on SERMs
  • STAR: a head-to-head comparison of tamoxifen and raloxifene as breast-cancer preventatives
  • Femarelle official site
  • Raloxifene (Evista) official site


This article was sourced from Creative Commons Attribution-ShareAlike License; additional terms may apply. World Heritage Encyclopedia content is assembled from numerous content providers, Open Access Publishing, and in compliance with The Fair Access to Science and Technology Research Act (FASTR), Wikimedia Foundation, Inc., Public Library of Science, The Encyclopedia of Life, Open Book Publishers (OBP), PubMed, U.S. National Library of Medicine, National Center for Biotechnology Information, U.S. National Library of Medicine, National Institutes of Health (NIH), U.S. Department of Health & Human Services, and USA.gov, which sources content from all federal, state, local, tribal, and territorial government publication portals (.gov, .mil, .edu). Funding for USA.gov and content contributors is made possible from the U.S. Congress, E-Government Act of 2002.
 
Crowd sourced content that is contributed to World Heritage Encyclopedia is peer reviewed and edited by our editorial staff to ensure quality scholarly research articles.
 
By using this site, you agree to the Terms of Use and Privacy Policy. World Heritage Encyclopedia™ is a registered trademark of the World Public Library Association, a non-profit organization.
 


Copyright © World Library Foundation. All rights reserved. eBooks from Project Gutenberg are sponsored by the World Library Foundation,
a 501c(4) Member's Support Non-Profit Organization, and is NOT affiliated with any governmental agency or department.