- 同
- 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 general term for female steroid sex hormones that are secreted by the ovary and responsible for typical female sexual characteristics (同)oestrogen
- 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
- エストロゲン(動物の雌を発情させる卵胞ホルモン)(《英》oestrogen)
- =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）』「2014/07/12 12:28:17」(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.
Contents
- 1 Members and uses
- 2 Mechanism of action
- 3 Actions
- 4 See also
- 5 References
- 6 External links
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 |
| 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 |
| ospemifene |
vaginal atrophy, dysparunia |
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 with some SERMs.
- Hot flashes are increased by some SERMs.
- Pituitary gland - clomifene blocks estrogen action, thus 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.
- ^ 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
|
Estrogenics
|
|
| 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.
|
|
|
| Other |
|
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
|
|
|
Procedures
|
- Adrenalectomy
- Hypophysectomy
- Oophorectomy
- Orchiectomy
|
|
|
|
Receptor antagonists: hormone antagonists
|
|
| Hypothalamic/pituitary axes |
|
Adrenal axis:
|
- Corticotropin releasing hormone antagonists
- Glucocorticoid antagonists
- Mineralocorticoid antagonists
- Selective glucocorticoid receptor agonist
|
|
|
Thyroid axis:
|
|
|
|
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
|
|
UpToDate Contents
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Japanese Journal
- 選択的エストロゲン受容体モジュレーター治療の進歩と今後の展開 (特集 骨粗鬆症 : 新たな骨粗鬆症治療薬と治療ストラテジー)
- 臨床 新規骨粗鬆症治療薬バゼドキシフェンの短期治療成績
- Effects of Selective Estrogen Receptor Modulators on Plasma Membrane Estrogen Receptors and Catecholamine Synthesis and Secretion in Cultured Bovine Adrenal Medullary Cells
- Inagaki Hirohide,Toyohira Yumiko,Takahashi Keita [他],Ueno Susumu,Obara Go,Kawagoe Toshinori,Tsutsui Masato,Hachisuga Toru,Yanagihara Nobuyuki
- Journal of Pharmacological Sciences 124(1), 66-75, 2014
- … We previously reported the occurrence and function of plasma membrane estrogen receptors in cultured bovine adrenal medullary cells. … Here we report the effects of raloxifene and tamoxifen, selective estrogen receptor modulators, on plasma membrane estrogen receptors and catecholamine synthesis and secretion in these cells. …
- NAID 130003382627
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 ...
- 17 Sep 2012 ... Selective estrogen receptor modulators, called SERMs for short, block the effects of estrogen in the breast tissue. SERMs work by sitting in the estrogen receptors in breast cells. If a SERM is in the estrogen receptor, there is no ...
Related Pictures
★リンクテーブル★
[★]
- 英
- raloxifene
- 化
- 塩酸ラロキシフェン raloxifene hydrochloride
- 同
- エビスタ
- 関
- 選択的エストロゲン受容体作動薬 selective estrogen receptor modulator SERM
[★]
- 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
[★]
- 英
- selective estrogen receptor modulator、SERM
- 関
- 選択的エストロゲン受容体調節因子
[★]
選択的エストロゲン受容体調節因子
- 関
- selective estrogen receptor modulator、SERM
[★]
選択的エストロゲン受容体調節薬 SERMs
[★]
選択的エストロゲン受容体調節薬
[★]
選択的エストロゲン受容体調節薬
[★]
- 関
- effect modifier、modifier
[★]
- 関
- choice、choose、elective、opt、option、optional、select、selection、selectively、selectivity
[★]
エストロゲン受容体 ER