選択的エストロゲン受容体調節因子
- 関
- selective estrogen receptor modulator、SERM
WordNet
- tending to select; characterized by careful choice; "an exceptionally quick and selective reader"- John Mason Brown
- characterized by very careful or fastidious selection; "the school was very selective in its admissions"
- 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
- 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
- =sense organ / 受信装置
- =estrogen
Wikipedia preview
出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/03/07 01:36:27」(JST)
[Wiki en表示]
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.
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Contents
- 1 Members and uses
- 2 Mechanism of action
- 3 Actions
- 4 See also
- 5 References
- 6 External links
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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 [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:
- 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
- ^ 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.
- ^ 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/S1470-2045(06)70911-1. 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. doi:10.1001/jama.288.3.321. PMID 12117397. http://jama.ama-assn.org/cgi/pmidlookup?view=long&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.
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
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Estrogenics
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|
| Receptor |
|
ER (α, β)
|
|
|
|
GPER
|
- Agonists: Estradiol
- Fulvestrant
- G-1
- Genistein
- Quercetin
- Tamoxifen
|
|
|
Enzyme
(inhibitors) |
|
20,22-Desmolase
|
- 22-ABC
- 3,3′-Dimethoxybenzidine
- 3-Methoxybenzidine
- Aminoglutethimide
- Cyanoketone
- Danazol
- Etomidate
- Mitotane
- Trilostane
|
|
|
17α-Hydroxylase,
17,20-Lyase
|
- 22-ABC
- 22-Oxime
- Abiraterone
- Bifonazole
- Clotrimazole
- Cyanoketone
- Cyproterone
- Danazol
- Econazole
- Galeterone
- Gestrinone
- Isoconazole
- Ketoconazole
- L-39
- Liarozole
- LY-207,320
- MDL-27,302
- Miconazole
- Mifepristone
- Orteronel
- Pioglitazone
- Rosiglitazone
- Spironolactone
- Stanozolol
- SU-10,603
- TGF-β
- Tioconazole
- Troglitazone
- VN/87-1
- YM116
|
|
|
3β-HSD
|
- 4-MA
- Azastene
- Cyanoketone
- Danazol
- Epostane
- Genistein
- Gestrinone
- Metyrapone
- Oxymetholone
- Pioglitazone
- Rosiglitazone
- Trilostane
- Troglitazone
|
|
|
17β-HSD
|
|
|
|
Aromatase
|
- 1,4,6-Androstatriene-3,17-dione
- 4-Androstene-3,6,17-trione
- 4-Cyclohexylaniline
- 4-Hydroxytestosterone
- 5α-DHNET
- Abyssinone II
- Aminoglutethimide
- Anastrozole
- Ascorbic acid (Vitamin C)
- Atamestane
- Bifonazole
- CGP-45,688
- CGS-47,645
- Clotrimazole
- DHT
- Difeconazole
- Econazole
- Exemestane
- Fadrozole
- Fenarimol
- Finrozole
- Formestane
- Imazalil
- Isoconazole
- Ketoconazole
- Letrozole
- Liarozole
- MEN-11066
- Miconazole
- Minamestane
- Nimorazole
- NKS01
- ORG-33,201
- Penconazole
- Plomestane
- Prochloraz
- Propioconazole
- Pyridoglutethimide
- Rogletimide
- Rotenone
- Talarozole
- Testolactone
- Tioconazole
- Triadimefon
- Triadimenol
- Troglitazone
- Vorozole
- YM511
- Zinc
Note: 5α-reductase and 21-hydroxylase inhibitors may also affect estrogen levels as they prevent metabolism of estrogen steroid precursors.
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|
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| Other |
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Endogenous
|
- Estrogens: 5α-Androstane-3β,17β-diol
- DHEA
- Estetrol
- Estradiol
- Estriol
- Estrone
- Antiestrogens: 2-Hydroxyestrone
- 16-Hydroxyestrone
- Precursors: Cholesterol
- 22R-Hydroxycholesterol
- 20α,22R-Dihydroxycholesterol
- Pregnenolone
- 17-Hydroxypregnenolone
- Progesterone
- 17-Hydroxyprogesterone
- Cortodoxone/Deoxycortisol
- DHEA
- DHEA sulfate
- 16-Hydroxy-DHEA
- 16-Hydroxy-DHEA sulfate
- Androstenediol
- Androstenedione
- 16-Hydroxyandrostenedione
- Testosterone
|
|
|
Indirect
|
- Androgens/Antiandrogens (see here)
- Calcitriol (a form of Vitamin D)
- GnRH agonists/antagonists (see here)
- Gonadotropins//Antigonadotropins (see here)
- Plasma proteins (SHBG, ABP, Albumin)
- Progestogens/Antiprogestins (see here)
- Prolactin
|
|
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Procedures
|
- Adrenalectomy
- Hypophysectomy
- Oophorectomy
- Orchiectomy
|
|
|
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Receptor antagonists: hormone antagonists
|
|
| Hypothalamic/pituitary axes |
Adrenal axis: Corticotropin releasing hormone antagonists - Glucocorticoid antagonists - Mineralocorticoid antagonists - Selective glucocorticoid receptor modulator
Thyroid axis: Antithyroid agents
Gonadal axis: Androgen antagonists - Antigonadotropins - Estrogen antagonists - Gonadotropin-releasing hormone antagonists - Progesterone antagonists - Selective androgen receptor modulator - Selective estrogen receptor modulator - Selective progesterone receptor modulator
|
|
| Eicosanoid |
Leukotriene antagonists - Prostaglandin antagonists
|
|
| Other |
Cholecystokinin antagonists
|
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UpToDate Contents
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English Journal
- Carcinogenicity and hormone studies with the tissue-selective estrogen receptor modulator bazadoxifene.
- Wright DJ, Earnhardt JN, Perry R, Bailey S, Komm B, Minck DR, Cukierski MA.SourceDrug Safety Research & Development, Pfizer, Groton, Connecticut. david.wright@pfizer.com.
- Journal of cellular physiology.J Cell Physiol.2013 Apr;228(4):724-33. doi: 10.1002/jcp.24219.
- Bazedoxifene Acetate (BZA) is a selective estrogen receptor modulator (SERM) that is approved for the prevention and/or treatment of osteoporosis in postmenopausal women. To assess for carcinogenic potential, BZA was administered ad libitum in the diet to rats for 2 years. BZA caused an increase in
- PMID 22949219
- The molecular mechanisms underlying the pharmacological actions of estrogens, SERMs and oxysterols: Implications for the treatment and prevention of osteoporosis.
- Nelson ER, Wardell SE, McDonnell DP.SourceDepartment of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC, USA.
- Bone.Bone.2013 Mar;53(1):42-50. doi: 10.1016/j.bone.2012.11.011. Epub 2012 Nov 17.
- Estrogen therapy and hormone therapy are effective options for the prevention and treatment of osteoporosis, although because of their significant side effect profile, long term use for these applications is not recommended. Whereas SERMs (Selective Estrogen Receptor Modulators) exhibit a more favor
- PMID 23168292
- Pharmacological characterization of an imidazolopyrazole as novel selective androgen receptor modulator.
- Zhang X, Allan GF, Tannenbaum P, Sbriscia T, Linton O, Lai MT, Haynes-Johnson D, Bhattacharjee S, Lundeen SG, Sui Z.SourceJanssen Research and Development LLC, Welsh&McKean Roads, Spring House, PA 19477, USA. Electronic address: xzhang5@its.jnj.com.
- The Journal of steroid biochemistry and molecular biology.J Steroid Biochem Mol Biol.2013 Mar;134:51-8. doi: 10.1016/j.jsbmb.2012.10.015. Epub 2012 Oct 23.
- Selective androgen receptor modulators (SARMs) are androgens with tissue-selective activity. SARMs that have anabolic activity on muscle while having minimal stimulatory activity on prostate are classified as SARM agonists. They can be used to prevent the loss of lean body mass that is associated wi
- PMID 23098693
Japanese Journal
- 6-Carboxymethyl genistein : a novel selective oestrogen receptor modulator (SERM) with unique, differential effects on the vasculature, bone and uterus
Related Links
- 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 ...
- Abstract. Selective oestrogen receptor modulators (SERMs) are structurally diverse non-steroidal compounds that bind to oestrogen receptors and produce oestrogen agonist effects in some tissues and oestrogen antagonist effects in others.
★リンクテーブル★
[★]
- 関
- selective estrogen receptor modulator、selective oestrogen receptor modulator
[★]
- 英
- selective estrogen receptor modulator、selective oestrogen receptor modulator、SERM
- 関
- 選択的エストロゲン受容体調節物質
[★]
- 関
- effect modifier、modifier
[★]
- 関
- choice、choose、elective、opt、option、optional、select、selection、selectively、selectivity
[★]
エストロゲン
- 関
- estrogen、estrogenic、female hormone、oestrogenic