| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Laboratories for Reproductive Biology and the Departments of
Pediatrics (J.A.K., E.L., C-i.W., E.M.W.), and Biochemistry and
Biophysics (E.L., E.M.W.) University of North Carolina Chapel
Hill North Carolina 27599
Endocrinology Branch (K.B.,
W.R.K.) Reproductive Toxicology Division National Health and
Environmental Effects Research Laboratory United States
Environmental Protection Agency Research Triangle Park, North
Carolina 27711
Natural and pharmacological androgen receptor (AR) ligands were tested for their ability to induce the AR NH2-terminal and carboxyl-terminal (N/C) interaction in a two-hybrid protein assay to determine whether N/C complex formation distinguishes in vivo AR agonists from antagonists. High-affinity agonists such as dihydrotestosterone, mibolerone, testosterone, and methyltrienolone at concentrations between 0.1 and 1 nM induce the N/C interaction more than 40-fold. The lower affinity anabolic steroids, oxandrolone and fluoxymesterone, require concentrations of 10–100 nM for up to 23-fold induction of the N/C interaction. However no N/C interaction was detected in the presence of the antagonists, hydroxyflutamide, cyproterone acetate, or RU56187, at concentrations up to 1 µM, or with 1 µM estradiol, progesterone, or medroxyprogesterone acetate; each of these steroids at 1–500 nM inhibited the dihydrotestosterone-induced N/C interaction, with medroxyprogesterone acetate being the most effective. In transient and stable cotransfection assays using the mouse mammary tumor virus reporter vector, all ligands displayed concentration-dependent AR agonist activity that paralleled induction of the N/C interaction, with antagonists and weaker agonists failing to induce the N/C interaction. AR dimerization and DNA binding in mobility shift assays and AR stabilization reflected, but were not dependent on, the N/C interaction. The results indicate that the N/C interaction facilitates agonist potency at low physiological ligand concentrations as detected in transcription, dimerization/DNA binding, and stabilization assays. However the N/C interaction is not required for agonist activity at sufficiently high ligand concentrations, nor does its inhibition imply antagonist activity.
This article has been cited by other articles:
 |
|
 |
|
  S. Lenie and J. Smitz Functional AR Signaling Is Evident in an In Vitro Mouse Follicle Culture Bioassay That Encompasses Most Stages of Folliculogenesis Biol Reprod, April 1, 2009; 80(4): 685 - 695. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Ma, W. Fu, P. Li, S. V. Nicosia, G. Jenster, X. Zhang, and W. Bai FoxO1 Mediates PTEN Suppression of Androgen Receptor N- and C-Terminal Interactions and Coactivator Recruitment Mol. Endocrinol., February 1, 2009; 23(2): 213 - 225. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. B Pippal and P. J Fuller Structure-function relationships in the mineralocorticoid receptor J. Mol. Endocrinol., December 1, 2008; 41(6): 405 - 413. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M. Centenera, J. M. Harris, W. D. Tilley, and L. M. Butler Minireview: The Contribution of Different Androgen Receptor Domains to Receptor Dimerization and Signaling Mol. Endocrinol., November 1, 2008; 22(11): 2373 - 2382. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Gogoi, M. Kudla, O. Gil, and D. Fishman The Activity of Medroxyprogesterone Acetate, an Androgenic Ligand, in Ovarian Cancer Cell Invasion Reproductive Sciences, October 1, 2008; 15(8): 846 - 852. [Abstract] [PDF]
|
|
|
|
|
|
S. D. Conzen Minireview: Nuclear Receptors and Breast Cancer Mol. Endocrinol., October 1, 2008; 22(10): 2215 - 2228. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Bai and E. M. Wilson Epidermal Growth Factor-Dependent Phosphorylation and Ubiquitinylation of MAGE-11 Regulates Its Interaction with the Androgen Receptor Mol. Cell. Biol., March 15, 2008; 28(6): 1947 - 1963. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. C. Hodgson, I. Astapova, A. N. Hollenberg, and S. P. Balk Activity of Androgen Receptor Antagonist Bicalutamide in Prostate Cancer Cells Is Independent of NCoR and SMRT Corepressors Cancer Res., September 1, 2007; 67(17): 8388 - 8395. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. B. Askew, R. T. Gampe Jr., T. B. Stanley, J. L. Faggart, and E. M. Wilson Modulation of Androgen Receptor Activation Function 2 by Testosterone and Dihydrotestosterone J. Biol. Chem., August 31, 2007; 282(35): 25801 - 25816. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. N. Birrell, L. M. Butler, J. M. Harris, G. Buchanan, and W. D. Tilley Disruption of androgen receptor signaling by synthetic progestins may increase risk of developing breast cancer FASEB J, August 1, 2007; 21(10): 2285 - 2293. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Lu, A. Wang, S. Lu, and Z. Dong A novel synthetic compound that interrupts androgen receptor signaling in human prostate cancer cells Mol. Cancer Ther., July 1, 2007; 6(7): 2057 - 2064. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Turgeon, M. C. Carr, P. M. Maki, M. E. Mendelsohn, and P. M. Wise Complex Actions of Sex Steroids in Adipose Tissue, the Cardiovascular System, and Brain: Insights from Basic Science and Clinical Studies Endocr. Rev., October 1, 2006; 27(6): 575 - 605. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Kazmin, T. Prytkova, C. E. Cook, R. Wolfinger, T.-M. Chu, D. Beratan, J. D. Norris, C.-y. Chang, and D. P. McDonnell Linking Ligand-Induced Alterations in Androgen Receptor Structure to Differential Gene Expression: A First Step in the Rational Design of Selective Androgen Receptor Modulators Mol. Endocrinol., June 1, 2006; 20(6): 1201 - 1217. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. He, R. T. Gampe Jr., A. T. Hnat, J. L. Faggart, J. T. Minges, F. S. French, and E. M. Wilson Probing the Functional Link between Androgen Receptor Coactivator and Ligand-binding Sites in Prostate Cancer and Androgen Insensitivity J. Biol. Chem., March 10, 2006; 281(10): 6648 - 6663. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Arlt Androgen therapy in women Eur. J. Endocrinol., January 1, 2006; 154(1): 1 - 11. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Buchanan, S. N. Birrell, A. A. Peters, T. Bianco-Miotto, K. Ramsay, E. J. Cops, M. Yang, J. M. Harris, H. A. Simila, N. L. Moore, et al. Decreased Androgen Receptor Levels and Receptor Function in Breast Cancer Contribute to the Failure of Response to Medroxyprogesterone Acetate Cancer Res., September 15, 2005; 65(18): 8487 - 8496. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Schaufele, X. Carbonell, M. Guerbadot, S. Borngraeber, M. S. Chapman, A. A. K. Ma, J. N. Miner, and M. I. Diamond The structural basis of androgen receptor activation: Intramolecular and intermolecular amino-carboxy interactions PNAS, July 12, 2005; 102(28): 9802 - 9807. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Bai, B. He, and E. M. Wilson Melanoma Antigen Gene Protein MAGE-11 Regulates Androgen Receptor Function by Modulating the Interdomain Interaction Mol. Cell. Biol., February 15, 2005; 25(4): 1238 - 1257. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-L. Hsu, Y.-L. Chen, H.-J. Ting, W.-J. Lin, Z. Yang, Y. Zhang, L. Wang, C.-T. Wu, H.-C. Chang, S. Yeh, et al. Androgen Receptor (AR) NH2- and COOH-Terminal Interactions Result in the Differential Influences on the AR-Mediated Transactivation and Cell Growth Mol. Endocrinol., February 1, 2005; 19(2): 350 - 361. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. R. Brown Nonsteroidal Selective Androgen Receptors Modulators (SARMs): Designer Androgens with Flexible Structures Provide Clinical Promise Endocrinology, December 1, 2004; 145(12): 5417 - 5419. [Full Text] [PDF]
|
|
|
|
|
|
D. Masiello, S.-Y. Chen, Y. Xu, M. C. Verhoeven, E. Choi, A. N. Hollenberg, and S. P. Balk Recruitment of {beta}-Catenin by Wild-Type or Mutant Androgen Receptors Correlates with Ligand-Stimulated Growth of Prostate Cancer Cells Mol. Endocrinol., October 1, 2004; 18(10): 2388 - 2401. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Shetty, C. C. Y. Weng, O. U. Bolden-Tiller, I. Huhtaniemi, D. J. Handelsman, and M. L. Meistrich Effects of Medroxyprogesterone and Estradiol on the Recovery of Spermatogenesis in Irradiated Rats Endocrinology, October 1, 2004; 145(10): 4461 - 4469. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Buchanan, M. Yang, A. Cheong, J. M. Harris, R. A. Irvine, P. F. Lambert, N. L. Moore, M. Raynor, P. J. Neufing, G. A. Coetzee, et al. Structural and functional consequences of glutamine tract variation in the androgen receptor Hum. Mol. Genet., August 15, 2004; 13(16): 1677 - 1692. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Hild, B. J. Attardi, and J. R. Reel The Ability of a Gonadotropin-Releasing Hormone Antagonist, Acyline, to Prevent Irreversible Infertility Induced by the Indenopyridine, CDB-4022, in Adult Male Rats: The Role of Testosterone Biol Reprod, July 1, 2004; 71(1): 348 - 358. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Pazol, M. E. Wilson, and K. Wallen Medroxyprogesterone Acetate Antagonizes the Effects of Estrogen Treatment on Social and Sexual Behavior in Female Macaques J. Clin. Endocrinol. Metab., June 1, 2004; 89(6): 2998 - 3006. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Wang, T. S. Udayakumar, T. S. Vasaitis, A. M. Brodie, and J. D. Fondell Mechanistic Relationship between Androgen Receptor Polyglutamine Tract Truncation and Androgen-dependent Transcriptional Hyperactivity in Prostate Cancer Cells J. Biol. Chem., April 23, 2004; 279(17): 17319 - 17328. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Sathya, C.-y. Chang, D. Kazmin, C. E. Cook, and D. P. McDonnell Pharmacological Uncoupling of Androgen Receptor-mediated Prostate Cancer Cell Proliferation and Prostate-specific Antigen Secretion Cancer Res., November 15, 2003; 63(22): 8029 - 8036. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. L. Amir, M. Barua, N. C. McKnight, S. Cheng, X. Yuan, and S. P. Balk A Direct {beta}-Catenin-independent Interaction between Androgen Receptor and T Cell Factor 4 J. Biol. Chem., August 15, 2003; 278(33): 30828 - 30834. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. U. Agoulnik, W. C. Krause, W. E. Bingman III, H. T. Rahman, M. Amrikachi, G. E. Ayala, and N. L. Weigel Repressors of Androgen and Progesterone Receptor Action J. Biol. Chem., August 15, 2003; 278(33): 31136 - 31148. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Terouanne, P. Nirde, F. Rabenoelina, W. Bourguet, C. Sultan, and G. Auzou Mutation of the Androgen Receptor at Amino Acid 708 (Glyright-arrowAla) Abolishes Partial Agonist Activity of Steroidal Antiandrogens Mol. Pharmacol., April 1, 2003; 63(4): 791 - 798. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. He and E. M. Wilson Electrostatic Modulation in Steroid Receptor Recruitment of LXXLL and FXXLF Motifs Mol. Cell. Biol., March 15, 2003; 23(6): 2135 - 2150. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Yin, Y. He, M. A. Perera, S. S. Hong, C. Marhefka, N. Stourman, L. Kirkovsky, D. D. Miller, and J. T. Dalton Key Structural Features of Nonsteroidal Ligands for Binding and Activation of the Androgen Receptor Mol. Pharmacol., January 1, 2003; 63(1): 211 - 223. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Y. Euling, C. Gennings, E. M. Wilson, J. A. Kemppainen, W. R. Kelce, and C. A. Kimmel Response-Surface Modeling of the Effect of 5{alpha}-Dihydrotestosterone and Androgen Receptor Levels on the Response to the Androgen Antagonist Vinclozolin Toxicol. Sci., October 1, 2002; 69(2): 332 - 343. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Masiello, S. Cheng, G. J. Bubley, M. L. Lu, and S. P. Balk Bicalutamide Functions as an Androgen Receptor Antagonist by Assembly of a Transcriptionally Inactive Receptor J. Biol. Chem., July 12, 2002; 277(29): 26321 - 26326. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Pawlowski, J. R. Ertel, M. P. Allen, M. Xu, C. Butler, E. M. Wilson, and M. E. Wierman Liganded Androgen Receptor Interaction with beta -Catenin. NUCLEAR CO-LOCALIZATION AND MODULATION OF TRANSCRIPTIONAL ACTIVITY IN NEURONAL CELLS J. Biol. Chem., May 31, 2002; 277(23): 20702 - 20710. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. S. Wilson, K. Bobseine, C. R. Lambright, and L. E. Gray Jr. A Novel Cell Line, MDA-kb2, That Stably Expresses an Androgen- and Glucocorticoid-Responsive Reporter for the Detection of Hormone Receptor Agonists and Antagonists Toxicol. Sci., March 1, 2002; 66(1): 69 - 81. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. C. Hartig, K. L. Bobseine, B. H. Britt, M. C. Cardon, C. R. Lambright, V. S. Wilson, and L. E. Gray Jr. Development of Two Androgen Receptor Assays Using Adenoviral Transduction of MMTV-Luc Reporter and/or hAR for Endocrine Screening Toxicol. Sci., March 1, 2002; 66(1): 82 - 90. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. M. Kuhn Anabolic Steroids Recent Prog. Horm. Res., January 1, 2002; 57(1): 411 - 434. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. He, N. T. Bowen, J. T. Minges, and E. M. Wilson Androgen-induced NH2- and COOH-terminal Interaction Inhibits p160 Coactivator Recruitment by Activation Function 2 J. Biol. Chem., November 2, 2001; 276(45): 42293 - 42301. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Nazarenko, S. D. Dertinger, and T. A. Gasiewicz In Vivo Antagonism of AhR-Mediated Gene Induction by 3'-Methoxy-4'-nitroflavone in TCDD-Responsive lacZ Mice Toxicol. Sci., June 1, 2001; 61(2): 256 - 264. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Raivio, J. J. Palvimo, L. Dunkel, S. Wickman, and O. A. Jänne Novel Assay for Determination of Androgen Bioactivity in Human Serum J. Clin. Endocrinol. Metab., March 1, 2001; 86(4): 1539 - 1544. [Abstract] [Full Text]
|
|
|
|
|
|
J. Kwong, J. W. Xuan, P. S. F. Chan, S.-M. Ho, and F. L. Chan A Comparative Study of Hormonal Regulation of Three Secretory Proteins (Prostatic Secretory Protein-PSP94, Probasin, and Seminal Vesicle Secretion II) in Rat Lateral Prostate Endocrinology, December 1, 2000; 141(12): 4543 - 4551. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Deplewski and R. L. Rosenfield Role of Hormones in Pilosebaceous Unit Development Endocr. Rev., August 1, 2000; 21(4): 363 - 392. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-a. Tan, S. H. Hall, K. G. Hamil, G. Grossman, P. Petrusz, J. Liao, K. Shuai, and F. S. French Protein Inhibitor of Activated STAT-1 (Signal Transducer and Activator of Transcription-1) Is a Nuclear Receptor Coregulator Expressed in Human Testis Mol. Endocrinol., January 1, 2000; 14(1): 14 - 26. [Abstract] [Full Text]
|
|
|
|
|
|
B. He, J. A. Kemppainen, J. J. Voegel, H. Gronemeyer, and E. M. Wilson Activation Function 2 in the Human Androgen Receptor Ligand Binding Domain Mediates Interdomain Communication with the NH2-terminal Domain J. Biol. Chem., December 24, 1999; 274(52): 37219 - 37225. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Poujol, J.-M. Wurtz, B. Tahiri, S. Lumbroso, J.-C. Nicolas, D. Moras, and C. Sultan Specific Recognition of Androgens by Their Nuclear Receptor. A STRUCTURE-FUNCTION STUDY J. Biol. Chem., July 28, 2000; 275(31): 24022 - 24031. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. He, J. A. Kemppainen, and E. M. Wilson FXXLF and WXXLF Sequences Mediate the NH2-terminal Interaction with the Ligand Binding Domain of the Androgen Receptor J. Biol. Chem., July 21, 2000; 275(30): 22986 - 22994. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
