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20-September-2008 09:55:50 - Selective estrogen receptor modulator Selective Estrogen Receptor Modulators SERMs are a class of medication that acts 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 scientificaly accepted SERMs from a botanical source. Contents 1 Members 2 Uses 3 Mechanism of action 4 Actions 5 References 6 See also 7 External links Members Members include: afimoxifene 4-hydroxytamoxifen arzoxifene bazedoxifene clomifene femarelle DT56a2 lasofoxifene ormeloxifene raloxifene tamoxifen toremifene Uses SERMs are used dependent on their pattern of action in various tissues: clomifene is used in anovulation femarelle is used for managing menopause symptoms and maintaining bone health ormeloxifene is used for contraception raloxifene is used for osteoporosis and reducing risk of invasive breast cancer tamoxifen and toremifene are used for breast cancer 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 increases the risk of breast cancer 3 and thrombosis.4 Some of the above agents still have significant side-effects to allow for widespread use. SERMs are also commonly used during PCT or Post Cycle Therapy after the use of anabolic steroids. Bodybuilders who take testosterone supplements will often experience gynecomastia, also known as man-boobs, after a steroid cycle, because the body will attempt to balance estrogen with increased testosterone levels. This increase in estrogen can produce gynecomastia, so body builders will usually cycle a SERM after a steroid cycle to ensure that their body is not flooded with excess estrogen. 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.56 Actions The actions of SERMs on various tissues: Bone turnover and postmenopausal osteoporosis respond favorably to most SERMs. 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. Uterus - tamoxifen may increase endometrial carcinoma risk, but raloxifene and femarelle do not. Data on toremifene and clomifene is insufficient. References ^ 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. doi:10.1056/NEJMc030651. PMID 12584371. ^ Somjen D, Katzburg S, Knoll E, Hendel D, Stern N, Kaye AM, Yoles I May 2007. DT56a Femarelle: a natural selective estrogen receptor modulator SERM. J. Steroid Biochem. Mol. Biol. 104 3-5: 252-8. doi:10.1016/j.jsbmb.2007.03.004. PMID 17428655. ^ 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. doi:10.1016/S1470-20450670911-1. PMID 17081916. ^ 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. PMID 12117397. ^ Shang Y, Brown M 2002. Molecular determinants for the tissue specificity of SERMs. Science 295 5564: 2465-8. doi:10.1126/science.1068537. PMID 11923541. ^ Smith CL, O'Malley BW 2004. Coregulator function: a key to understanding tissue specificity of selective receptor modulators. Endocr Rev 25 1: 45-71. doi:10.1210/er.2003-0023. PMID 14769827. See also Selective androgen receptor modulator Selective progesterone receptor modulator Phytoserm Femarelle Lasofoxifene Ormeloxifene Raloxifene Tamoxifen Toremifene 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 v d e Sex hormones and related agents primarily G03, also L02, H01C - human endogenous in CAPS Progestogens: receptor Agonist PROGESTERONE, Dienogest, Desogestrel, Drospirenone, Dydrogesterone, Ethisterone, Etonogestrel, Ethynodiol diacetate, Gestodene, Gestonorone, Levonorgestrel, Lynestrenol, Medroxyprogesterone, Megestrol, Norelgestromin, Norethisterone, Norethynodrel, Norgestimate, Norgestrel, Norgestrienone, Tibolone SPRM Asoprisnil, CDB-4124 Antiprogestogen Mifepristone Androgens: receptor Agonist TESTOSTERONE, Androstanolone, Fluoxymesterone, Mesterolone, Methyltestosterone, see also anabolic steroids Antiandrogen Bicalutamide, Cyproterone, Dienogest, Flutamide, Nilutamide, Spironolactone Estrogens: receptor Agonist ESTRADIOL, ESTRIOL, ESTRONE, Chlorotrianisene, Dienestrol, Diethylstilbestrol, Ethinylestradiol, Fosfestrol, Mestranol, Polyestradiol phosphate SERM Afimoxifene, Arzoxifene, Bazedoxifene, Clomifene, Fulvestrant, Lasofoxifene, Raloxifene, Tamoxifen, Toremifene AI Aminoglutethimide, Anastrozole, Atamestane, Exemestane, Fadrozole, Formestane, Letrozole, Vorozole Antiestrogen Mepitiostane Gonadotropins: FSHR/LHCGR ovulation stim. Clomifene, Urofollitropin Antigonadotropin Danazol, Gestrinone GnRH: receptor Agonist Buserelin, Goserelin, Histrelin, Leuprorelin, Nafarelin, Triptorelin Antagonist Abarelix, Cetrorelix, Ganirelix v d e Receptor antagonists: hormone antagonists Hypothalamic/pituitary axes Adrenal axis: Corticotropin releasing hormone antagonists - Aldosterone antagonists Thyroid axis: Antithyroid agents Gonadal axis: Androgen antagonists - Gonadotropin-releasing hormone antagonists - Selective estrogen receptor modulator Eicosanoid Leukotriene antagonists - Prostaglandin antagonists Other Cholecystokinin antagonists Retrieved from http://en..org/wiki/Selective_estrogen_receptor_modulator Categories: Drugs | Receptor modulators | Selective estrogen receptor modulators Views Article Discussion this page History Personal tools Log in / create account Navigation Main page Contents Featured content Current events Random article Search Go Search Interaction Community portal Recent changes Contact Donate to Help Toolbox What links here Related changes Upload file Special pages Printable version Permanent link Cite this page Languages Deutsch Português Italiano This page was last modified on 12 August 2008, at 08:32
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