The nongenotropic synthetic ligand 4-estren-3α17β-diol is a high-affinity genotropic androgen receptor agonist

Molecular Pharmacology

Volumn 67, Issue 3, 2005, Pages 744-748

  Krishnan, V ^a   Bullock, H A ^a   Yaden, B C ^a   Liu, M ^a   Barr, R J ^a   Montrose Rafizadeh, C ^a   Chen, K ^a   Dodge, J A ^a   Bryant, H U ^a  

^a ELI LILLY AND COMPANY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1,4 DIAMINO 1,4 BIS(2 AMINOPHENYLTHIO) 2,3 DICYANOBUTADIENE; 4 ESTREN 3ALPHA17BETA DIOL; ANDROGEN; ANDROGEN RECEPTOR; BICALUTAMIDE; ESTRANE DERIVATIVE; ESTROGEN RECEPTOR ALPHA; ESTROGEN RECEPTOR BETA; FULVESTRANT; LUCIFERASE; PROSTATE SPECIFIC ANTIGEN; UNCLASSIFIED DRUG; WORTMANNIN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIGEN EXPRESSION; ARTICLE; BINDING AFFINITY; CHROMATIN; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG EFFECT; DRUG EFFICACY; DRUG INHIBITION; DRUG MECHANISM; DRUG RECEPTOR BINDING; ENZYME ACTIVITY; FEMALE; GENE TARGETING; HUMAN; HUMAN CELL; IMMUNOPRECIPITATION; IN VIVO STUDY; LEVATOR ANI MUSCLE; MALE; MOUSE; NONHUMAN; ORCHIECTOMY; PRIORITY JOURNAL; PROMOTER REGION; RAT; SEMINAL VESICLE; TARGET ORGAN;

CELL LINE, TUMOR; ENZYME-LINKED IMMUNOSORBENT ASSAY; ESTRENES; HUMANS; INSULIN-LIKE GROWTH FACTOR I; KINETICS; MALE; PROSTATE-SPECIFIC ANTIGEN; PROSTATIC NEOPLASMS; PROTEIN TRANSPORT; RECEPTORS, ANDROGEN; RECOMBINANT PROTEINS; RNA, MESSENGER; TRANSFECTION;

EID: 14944350977     PISSN: 0026895X     EISSN: None     Source Type: Journal    
DOI: 10.1124/mol.104.005272     Document Type: Article

References (18)

1. Centrella M, McCarthy TL, Chang W-Z, Labaree DC, and Hochberg RB (2004) Estren (4-estren-3α,17β-diol) is a prohormone that regulates both androgenic and estrogenic transcriptional effects through the androgen receptor. Mol Endocrinol 18:1120-1130.
2. Cleutjens KB, van Eekelen CC, van der Korput HA, Brinkmann AO, and Trapman J (1996) Two androgen response regions cooperate in steroid hormone regulated activity of the prostate-specific antigen promoter. J Biol Chem 271:6379-6388.
3. Frasor J, Barnett DH, Danes JM, Hess R, Parlow AF, and Katzenellenbogen BS (2003) Response-specific and ligand dose-dependent modulation of estrogen receptor (ER) alpha activity by ERbeta in the uterus. Endocrinology 144:3159-3166.
4. Harris HA, Katzenellenbogen JA, and Katzenellenbogen BS (2002) Characterization of the biological roles of the estrogen receptors, ERα and ERβ, in estrogen target tissues in vivo through the use of an ERα-selective ligand. Endocrinology 143:4172-4177.
5. Jenster G, Trapman J, and Brinkmann AO (1993) Nuclear import of the human androgen receptor. Biochem J 293:761-768.
6. Kato S, Kitamoto T, Masuhiro Y, and Yanagisawa J (1998) Molecular mechanism of a cross-talk between estrogen and growth-factor signaling pathways. Oncology 55:5-10.
7. Kousteni S, Bellido T, Plotkin LI, O'Brien CA, Bodenner DL, Han L, Han K, DiGregorio GB, Katzenellenbogen JA, Katzenellenbogen BS, et al. (2001) Non-genotropic, sex-nonspecific signaling through the estrogen or androgen receptors: dissociation from transcriptional activity. Cell 104:719-730.
8. Kousteni S, Chen JR, Bellido T, Han L, Ali AA, O'Brien CA, Plotkin L, Fu Q, Mancino AT, Wen Y, et al. (2002) Reversal of bone loss in mice by nongenotropic signaling of sex steroids [published erratum in Science (Wash DC) 299:1184, 2003]. Science (Wash DC) 298:843-846.
9. Kousteni S, Han L, Chen JR, Almeida M, Plotkin LI, Bellido T, and Manolagas SC (2003) Kinase-mediated regulation of common transcription factors accounts for the bone-protective effects of sex steroids. J Clin Investig 111:1651-1664.
10. Krieg M (1976) Characterization of the androgen receptor in the skeletal muscle of the rat. Steroids 28:261-274.
11. Luke MC and Coffey DS (1994) Human androgen receptor binding to the androgen response element of prostate specific antigen. J Androl 15:41-51.
12. Merchenthaler I, Funkhouser JM, Carver JM, Lundeen SG, Ghosh K, and Winneker RC (1998) The effect of estrogens and antiestrogens in a rat model for hot flush. Maturitas 30:307-316.
13. Nnodim JO (2001) Testosterone mediates satellite cell activation in denervated rat levator ani muscle. Anat Rec 263:19-24.
14. Panidis D, Vavilis D, Rousso D, Stergiopoulos K, and Kalogeropoulos A (1994) Danazol influences gonadotropin secretion acting at the hypothalamic level. Int J Gynaecol Obstet 45:241-246.
15. Shang Y, Brown M, and Brown M (2002) Formation of the androgen receptor transcription complex. Mol Cell 9:601-610.
16. Simoncini T, Hafezi-Moghadam A, Brazil DP, Ley K, Chin WW, and Liao JK (2000) Interaction of oestrogen receptor with the regulatory subunit of phosphatidylinositol-3-OH kinase. Nature (Lond) 407:538-541.
17. Simpkins JW, Katovich M, and Song I-C (1983) Similarities between morphine withdrawal in the rat and the menopausal hot flush. Life Sci 32:1957-1966.
18. Turner RT, Wakley GK, and Hannon KS (1990) Differential effects of androgens on cortical bone histomorphometry in gonadectomized male and female rats. J Orthop Res 8:612-617.