雄激素受體

雄激素受體(英語:androgen receptor,簡稱為AR),亦被稱為NR3C4(核受體亞家族3,C組,成員4)是一類核受體[6],當雄性激素睾酮二氫睾酮[7]在細胞質中與之結合後會使之激活繼而轉運進核內。雄激素受體與孕酮受體之間的關係很密切,高劑量的黃體製劑可阻斷雄激素受體[8][9]

雄激素受體
雄激素受體(彩虹卡通圖)結合配體的結構域正與睾酮(白色棍狀)結合的晶體結構[1]
有效結構
PDB 直系同源檢索:PDBe, RCSB
標識
代號 AR; AIS; DHTR; HUMARA; HYSP1; KD; NR3C4; SBMA; SMAX1; TFM
擴展標識 遺傳學313700 鼠基因88064 同源基因28 IUPHAR:   ChEMBL: 1871 GeneCards: AR Gene
RNA表達模式
更多表達數據
直系同源體
物種 人類 小鼠
Entrez 367 11835
Ensembl ENSG00000169083 ENSMUSG00000046532
UniProt P10275 P19091
mRNA序列 NM_000044 NM_013476
蛋白序列 NP_000035 NP_038504
基因位置 Chr X:
66.76 – 66.95 Mb
Chr X:
98.15 – 98.32 Mb
PubMed查詢 [1] [2]
雄激素受體
人類雄激素受體結合配體的結構域正與雄激素結合的晶體結構,受體NH2-端肽鏈、ar20-30及r1881
鑑定
標誌Androgen_recep
PfamPF02166舊版
InterPro英語InterProIPR001103
雄激素受體的正常功能。如果細胞中存在5α-還原酶,睾酮(T)進入細胞後就會被轉化為二氫睾酮(DHT)。雄激素受體(AR)一旦與甾體結合後就會發生構象改變並釋放一些熱休克蛋白(hsps)。在甾體結合之前或之後會發生磷酸化(P)。AR轉運到細胞核中,在那裏會相互之間形成二聚體、與DNA結合併招募共激活因子。靶基因被轉錄(mRNA)繼而被翻譯為蛋白質[2][3][4][5]

雄激素受體的主要功能是作為調控基因表達的一種結合DNA的轉錄因子[10];然而雄激素受體也有其它方面的功能[11]。受雄激素調控的基因在男性性表型的發育及維持中起到重要作用。

另見

參考文獻

  1. ^ PDB 2AM9; Pereira de Jésus-Tran K, Côté PL, Cantin L, Blanchet J, Labrie F, Breton R. Comparison of crystal structures of human androgen receptor ligand-binding domain complexed with various agonists reveals molecular determinants responsible for binding affinity. Protein Sci. May 2006, 15 (5): 987–99. PMC 2242507 . PMID 16641486. doi:10.1110/ps.051905906. 
  2. ^ Quigley CA, De Bellis A, Marschke KB, el-Awady MK, Wilson EM, French FS. Androgen receptor defects: historical, clinical, and molecular perspectives. Endocr. Rev. June 1995, 16 (3): 271–321. PMID 7671849. doi:10.1210/edrv-16-3-271. 
  3. ^ Gottlieb B, Lombroso R, Beitel LK, Trifiro MA. Molecular pathology of the androgen receptor in male (in)fertility. Reprod. Biomed. Online. January 2005, 10 (1): 42–8. PMID 15705293. doi:10.1016/S1472-6483(10)60802-4. 
  4. ^ Choong CS, Wilson EM. Trinucleotide repeats in the human androgen receptor: a molecular basis for disease. J. Mol. Endocrinol. December 1998, 21 (3): 235–57. PMID 9845666. doi:10.1677/jme.0.0210235. 
  5. ^ Meehan KL, Sadar MD. Androgens and androgen receptor in prostate and ovarian malignancies. Front. Biosci. May 2003, 8: d780–800. PMID 12700055. doi:10.2741/1063. 
  6. ^ Lu NZ, Wardell SE, Burnstein KL, Defranco D, Fuller PJ, Giguere V, Hochberg RB, McKay L, Renoir JM, Weigel NL, Wilson EM, McDonnell DP, Cidlowski JA. International Union of Pharmacology. LXV. The pharmacology and classification of the nuclear receptor superfamily: glucocorticoid, mineralocorticoid, progesterone, and androgen receptors. Pharmacol. Rev. December 2006, 58 (4): 782–97. PMID 17132855. doi:10.1124/pr.58.4.9. 
  7. ^ Roy AK, Lavrovsky Y, Song CS, Chen S, Jung MH, Velu NK, Bi BY, Chatterjee B. Regulation of androgen action. Vitam. Horm. Vitamins & Hormones. 1999, 55: 309–52. ISBN 978-0-12-709855-5. PMID 9949684. doi:10.1016/S0083-6729(08)60938-3. 
  8. ^ Bardin CW, Brown T, Isomaa VV, Jänne OA. Progestins can mimic, inhibit and potentiate the actions of androgens. Pharmacol. Ther. 1983, 23 (3): 443–59. PMID 6371845. doi:10.1016/0163-7258(83)90023-2. 
  9. ^ Raudrant D, Rabe T. Progestogens with antiandrogenic properties. Drugs. 2003, 63 (5): 463–92. PMID 12600226. doi:10.2165/00003495-200363050-00003. [永久失效連結]
  10. ^ Mooradian AD, Morley JE, Korenman SG. Biological actions of androgens. Endocr. Rev. 1987, 8 (1): 1–28. PMID 3549275. doi:10.1210/edrv-8-1-1. 
  11. ^ Heinlein CA, Chang C. The roles of androgen receptors and androgen-binding proteins in nongenomic androgen actions. Mol. Endocrinol. 2002, 16 (10): 2181–7. PMID 12351684. doi:10.1210/me.2002-0070. 

外部連結