selective estrogen-receptor modulator

選択的エストロゲン受容体調節薬

WordNet

1. tending to select; characterized by careful choice; "an exceptionally quick and selective reader"- John Mason Brown
2. characterized by very careful or fastidious selection; "the school was very selective in its admissions"
3. a general term for female steroid sex hormones that are secreted by the ovary and responsible for typical female sexual characteristics (同)oestrogen
4. a cellular structure that is postulated to exist in order to mediate between a chemical agent that acts on nervous tissue and the physiological response

PrepTutorEJDIC

1. 選択の,染択する / 注意して選ばれた / 淘汰(とうた)の / (無線が)選択度の高い
2. エストロゲン(動物の雌を発情させる卵胞ホルモン)(《英》oestrogen)
3. =sense organ / 受信装置

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/01/08 12:39:01」(JST)

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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.

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	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 and thrombosis. 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.

Actions

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.

See also

• Selective receptor modulator
• Selective androgen receptor modulator
• Selective progesterone receptor modulator
• Selective glucocorticoid receptor agonist

References

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

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

• 1. 選択的エストロゲン受容体モジュレーターの作用機序 mechanisms of action of selective estrogen receptor modulators
• 2. 骨粗鬆症に対する選択的エストロゲン受容体調節剤 selective estrogen receptor modulators for osteoporosis
• 3. 乳癌予防のための選択的エストロゲン受容体調節因子およびアロマターゼ阻害剤 selective estrogen receptor modulators and aromatase inhibitors for breast cancer prevention
• 4. 転移性乳癌の全身治療：内分泌療法 systemic treatment for metastatic breast cancer endocrine therapy
• 5. タモキシフェンの副作用管理 managing the side effects of tamoxifen

English Journal

• Androgens and estrogens in benign prostatic hyperplasia: Past, present and future.

• Nicholson TM, Ricke WA.SourceUniversity of Rochester School of Medicine & Dentistry, Rochester, NY, United States.
• Differentiation; research in biological diversity.Differentiation.2011 Nov-Dec;82(4-5):184-99. Epub 2011 May 26.
• Benign prostatic hyperplasia (BPH) and associated lower urinary tract symptoms (LUTS) are common clinical problems in urology. While the precise molecular etiology remains unclear, sex steroids have been implicated in the development and maintenance of BPH. Sufficient data exists linking androgens a
• PMID 21620560

Japanese Journal

• Dysfunction of fibroblasts of extrarenal origin underlies renal fibrosis and renal anemia in mice

• Asada Nariaki,Takase Masayuki,Nakamura Jin,Oguchi Akiko,Asada Misako,Suzuki Norio,Yamamura Ken-ichi,Nagoshi Narihito,Shibata Shinsuke,Rao Tata Nageswara,Fehling Hans Joerg,Fukatsu Atsushi,Minegishi Naoko,Kita Toru,Kimura Takeshi,Okano Hideyuki,Yamamoto Masayuki,Yanagita Motoko
• Journal of Clinical Investigation, 2011-09-12
• … Moreover, the in vivo administration oftamoxifen, a selective estrogen receptor modulator, restored attenuated erythropoietin production as well asfibrosis in a mouse model of kidney fibrosis. …
• NAID 120003338854

Related Links

• Selective estrogen receptor modulator - Wikipedia, the free ...

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 ...

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「選択的エストロゲン受容体調節薬」

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英

selective estrogen-receptor modulator, selective estrogen-receptor modulators SERMs

関

エストロゲン受容体、エストロゲン

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「selective estrogen-receptor modulators」

　　[★] 選択的エストロゲン受容体調節薬 SERMs

「modulator」

　　[★]

• n.

• 修飾因子、修飾物質、(受容体等へのアロステリック結合によりアゴニスト作用を変化させる薬剤)修飾薬、モジュレーター、変調器

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effect modifier、modifier

「selective」

　　[★]

• adj.

• 選択的な、選択性の、選択の

関

choice、choose、elective、opt、option、optional、select、selection、selectively、selectivity

　 　 　

「estrogen receptor」

　　[★] エストロゲン受容体 ER