Mechanism of the tissue-specific action of the selective androgen receptor modulator s-101479

Biological and Pharmaceutical Bulletin

Volumn 36, Issue 3, 2013, Pages 442-451

  Furuya, Kazuyuki ^a,b   Yamamoto, Noriko ^a   Ohyabu, Yuki ^a   Morikyu, Teruyuki ^a   Ishige, Hirohide ^a   Albers, Michael ^c   Endob, Yasuhisa ^b  

^a KAKEN PHARMACEUTICAL CO LTD   (Japan)

^b KYOTO INSTITUTE OF TECHNOLOGY   (Japan)

^c PHENEX PHARMACEUTICALS AG   (Germany)

Author keywords

Bone; Cofactor; Dimerization; Osteoblast; Selective androgen receptor modulator

Indexed keywords

ALKALINE PHOSPHATASE BONE ISOENZYME; ANDROGEN RECEPTOR; ANDROSTANOLONE; BETA CATENIN; BICALUTAMIDE; BMS 564929; GELSOLIN; NUCLEAR RECEPTOR COACTIVATOR 2; PROTEIN P160; S 101479; S 49288; SELECTIVE ANDROGEN RECEPTOR MODULATOR; STANOZOLOL; STEROID RECEPTOR COACTIVATOR 1; STEROID RECEPTOR COACTIVATOR 3; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR PROX1; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL TISSUE; ARTICLE; BIOSYNTHESIS; BONE MINERAL; BONE TISSUE; CONCENTRATION RESPONSE; CONTROLLED STUDY; DIMERIZATION; DRUG STRUCTURE; ENDOMETRIUM; ENZYME ACTIVITY; FEMALE; GENETIC TRANSCRIPTION; MOUSE; NEWBORN; NONHUMAN; OSTEOBLAST; OVARIECTOMY; PROTEIN TRANSPORT; RECEPTOR BINDING; RECEPTOR UPREGULATION; TISSUE SPECIFICITY; TWO HYBRID SYSTEM; UTERUS WEIGHT;

ANIMALS; BENZOFURANS; CELL DIFFERENTIATION; DIHYDROTESTOSTERONE; FEMALE; ORGAN SPECIFICITY; OSTEOBLASTS; OVARIECTOMY; PROTEIN MULTIMERIZATION; QUINOLINES; RATS; RATS, SPRAGUE-DAWLEY; RECEPTORS, ANDROGEN; TRANSCRIPTIONAL ACTIVATION;

EID: 84875519951     PISSN: 09186158     EISSN: 13475215     Source Type: Journal    
DOI: 10.1248/bpb.b12-00885     Document Type: Article

References (55)

1. Katznelson L, Finkelstein JS, Schoenfeld DA, Rosenthal DI, Anderson EJ, Klibanski A. Increase in bone density and lean body mass during testosterone administration in men with acquired hypogonadism. J. Clin. Endocrinol. Metab., 81, 4358-4365 (1996).
2. Shahani S, Braga-Basaria M, Maggio M, Basaria S. Androgens and erythropoiesis: Past and present. J. Endocrinol. Invest., 32, 704-716 (2009).
3. Rhoden EL, Morgentaler A. Risks of testosterone-replacement therapy and recommendations for monitoring. N. Engl. J. Med., 350, 482-492 (2004).
4. Davis SR, Tran J. Testosterone influences libido and well being in women. Trends Endocrinol. Metab., 12, 33-37 (2001).
5. Redmond GP. Androgens and women's health. Int. J. Fertil. Womens Med., 43, 91-97 (1998).
6. Chesnut CH 3rd, Ivey JL, Gruber HE, Matthews M, Nelp WB, Sisom K, Baylink DJ. Stanozolol in postmenopausal osteoporosis: Therapeutic efficacy and possible mechanisms of action. Metabolism, 32, 571-580 (1983).
7. Ishak KG, Zimmerman HJ. Hepatotoxic effects of the anabolic/androgenic steroids. Semin. Liver Dis., 7, 230-236 (1987).
8. Hanada K, Furuya K, Yamamoto N, Nejishima H, Ichikawa K, Nakamura T, Miyakawa M, Amano S, Sumita Y, Oguro N. Bone anabolic effects of S-40503, a novel nonsteroidal selective androgen receptor modulator (SARM), in rat models of osteoporosis. Biol. Pharm. Bull., 26, 1563-1569 (2003).
9. Ostrowski J, Kuhns JE, Lupisella JA, Manfredi MC, Beehler BC, Krystek SR Jr, Bi Y, Sun C, Seethala R, Golla R, Sleph PG, Fura A, An Y, Kish KF, Sack JS, Mookhtiar KA, Grover GJ, Hamann LG. Pharmacological and X-ray structural characterization of a novel selective androgen receptor modulator: Potent hyperanabolic stimulation of skeletal muscle with hypostimulation of prostate in rats. Endocrinology, 148, 4-12 (2007).
10. Gao W, Kearbey JD, Nair VA, Chung K, Parlow AF, Miller DD, Dalton JT. Comparison of the pharmacological effects of a novel selective androgen receptor modulator, the 5alpha-reductase inhibitor finasteride, and the antiandrogen hydroxyflutamide in intact rats: New approach for benign prostate hyperplasia. Endocrinology, 145, 5420-5428 (2004).
11. Miner JN, Chang W, Chapman MS, Finn PD, Hong MH, López FJ, Marschke KB, Rosen J, Schrader W, Turner R, van Oeveren A, Viveros H, Zhi L, Negro-Vilar A. An orally active selective androgen receptor modulator is efficacious on bone, muscle, and sex function with reduced impact on prostate. Endocrinology, 148, 363-373 (2007).
12. Schmidt A, Harada S, Kimmel DB, Bai C, Chen F, Rutledge SJ, Vogel RL, Scafonas A, Gentile MA, Nantermet PV, McElwee-Witmer S, Pennypacker B, Masarachia P, Sahoo SP, Kim Y, Meissner RS, Hartman GD, Duggan ME, Rodan GA, Towler DA, Ray WJ. Identification of anabolic selective androgen receptor modulators with reduced activities in reproductive tissues and sebaceous glands. J. Biol. Chem., 284, 36367-36376 (2009).
13. Furuya K, Yamamoto N, Ohyabu Y, Makino A, Morikyu T, Ishige H, Kuzutani K, Endo Y. The novel non-steroidal selective androgen receptor modulator S-101479 has additive effects with bisphosphonate, selective estrogen receptor modulator, and parathyroid hormone on the bones of osteoporotic female rats. Biol. Pharm. Bull., 35, 1096-1104 (2012).
14. L ee DK, Chang C. Molecular communication between androgen receptor and general transcription machinery. J. Steroid Biochem. Mol. Biol., 84, 41-49 (2003).
15. Heemers HV, Tindall DJ. Androgen receptor (AR) coregulators: A diversity of functions converging on and regulating the AR transcriptional complex. Endocr. Rev., 28, 778-808 (2007).
16. Shibata H, Spencer TE, Onate SA, Jenster G, Tsai SY, Tsai MJ, O'Malley BW. Role of co-activators and co-repressors in the mechanism of steroid/thyroid receptor action. Recent Prog. Horm. Res., 52, 141-165 (1997).
17. Wong C, Kelce WR, Sar M, Wilson EM. Androgen receptor antagonist versus agonist activities of the fungicide vinclozolin relative to hydroxyflutamide. J. Biol. Chem., 270, 19998-20003 (1995).
18. Kallio PJ, Poukka H, Moilanen A, Jänne OA, Palvimo JJ. Androgen receptor-mediated transcriptional regulation in the absence of direct interaction with a specific DNA element. Mol. Endocrinol., 9, 1017-1028 (1995).
19. Brzozowski AM, Pike ACW, Dauter Z, Hubbard RE, Bonn T, Engström O, Ohman L, Greene GL, Gustafsson JA, Carlquist M. Molecular basis of agonism and antagonism in the oestrogen receptor. Nature, 389, 753-758 (1997).
20. Kumar V, Chambon P. The estrogen receptor binds tightly to its responsive element as a ligand-induced homodimer. Cell, 55, 145-156 (1988). 21) L onard DM, Lanz RB, O'Malley BW. Nuclear receptor coregulators and human disease. Endocr. Rev., 28, 575-587 (2007).
21. Schmidt A, Kimmel DB, Bai C, Scafonas A, Rutledge S, Vogel RL, McElwee-Witmer S, Chen F, Nantermet PV, Kasparcova V, Leu CT, Zhang HZ, Duggan ME, Gentile MA, Hodor P, Pennypacker B, Masarachia P, Opas EE, Adamski SA, Cusick TE, Wang J, Mitchell HJ, Kim Y, Prueksaritanont T, Perkins JJ, Meissner RS, Hartman GD, Freedman LP, Harada S, Ray WJ. Discovery of the selective androgen receptor modulator MK-0773 using a rational development strategy based on differential transcriptional requirements for androgenic anabolism versus reproductive physiology. J. Biol. Chem., 285, 17054-17064 (2010).
22. Sudo H, Kodama HA, Amagai Y, Yamamoto S, Kasai S. In vitro differentiation and calcification in a new clonal osteogenic cell line derived from newborn mouse calvaria. J. Cell Biol., 96, 191-198 (1983).
23. Clover J, Gowen M. Are MG-63 and HOS TE85 human osteosarcoma cell lines representative models of the osteoblastic phenotype? Bone, 15, 585-591 (1994).
24. Yamamoto N, Furuya K, Hanada K. Progressive development of the osteoblast phenotype during differentiation of osteoprogenitor cells derived from fetal rat calvaria: Model for in vitro bone formation. Biol. Pharm. Bull., 25, 509-515 (2002).
25. Schiller PC, D'Ippolito G, Roos BA, Howard GA. Anabolic or catabolic responses of MC3T3-E1 osteoblastic cells to parathyroid hormone depend on time and duration of treatment. J. Bone Miner. Res., 14, 1504-1512 (1999).
26. Abu EO, Horner A, Kusec V, Triffitt JT, Compston JE. The localization of androgen receptors in human bone. J. Clin. Endocrinol. Metab., 82, 3493-3497 (1997).
27. van der Eerden BC, van Til NP, Brinkmann AO, Lowik CW, Wit JM, Karperien M. Gender differences in expression of androgen receptor in tibial growth plate and metaphyseal bone of the rat. Bone, 30, 891-896 (2002).
28. He B, Kemppainen JA, Wilson EM. FXXLF and WXXLF sequences mediate the NH2-terminal interaction with the ligand binding domain of the androgen receptor. J. Biol. Chem., 275, 22986-22994 (2000).
29. Ikonen T, Palvimo JJ, Jänne OA. Interaction between the aminoand carboxyl-terminal regions of the rat androgen receptor modulates transcriptional activity and is influenced by nuclear receptor coactivators. J. Biol. Chem., 272, 29821-29828 (1997).
30. Gottlieb B, Lehväslaiho H, Beitel LK, Lumbroso R, Pinsky L, Trifiro M. The androgen receptor gene mutations database. Nucleic Acids Res., 26, 234-238 (1998).
31. Thompson J, Saatcioglu F, Jänne OA, Palvimo JJ. Disrupted aminoand carboxyl-terminal interactions of the androgen receptor are linked to androgen insensitivity. Mol. Endocrinol., 15, 923-935 (2001).
32. Smith CL, O'Malley BW. Coregulator function: A key to understanding tissue specificity of selective receptor modulators. Endocr. Rev., 25, 45-71 (2004).
33. Shang Y, Brown M. Molecular determinants for the tissue specificity of SERMs. Science, 295, 2465-2468 (2002).
34. Yang F, Li X, Sharma M, Sasaki CY, Longo DL, Lim B, Sun Z. Linking beta-catenin to androgen-signaling pathway. J. Biol. Chem., 277, 11336-11344 (2002).
35. Pawlowski JE, Ertel JR, Allen MP, Xu M, Butler C, Wilson EM, Wierman ME. Liganded androgen receptor interaction with betacatenin: Nuclear co-localization and modulation of transcriptional activity in neuronal cells. J. Biol. Chem., 277, 20702-20710 (2002).
36. Gaur T, Lengner CJ, Hovhannisyan H, Bhat RA, Bodine PV, Komm BS, Javed A, van Wijnen AJ, Stein JL, Stein GS, Lian JB. Canonical WNT signaling promotes osteogenesis by directly stimulating Runx2 gene expression. J. Biol. Chem., 280, 33132-33140 (2005).
37. Krishnan V, Bryant HU, MacDougald OA. Regulation of bone mass by Wnt signaling. J. Clin. Invest., 116, 1202-1209 (2006).
38. L iu XH, Kirschenbaum A, Yao S, Levine AC. Androgens promote preosteoblast differentiation via activation of the canonical Wnt signaling pathway. Ann. N. Y. Acad. Sci., 1116, 423-431 (2007).
39. Balmer NN, Richer JK, Spoelstra NS, Torkko KC, Lyle PL, Singh M. Steroid receptor coactivator AIB1 in endometrial carcinoma, hyperplasia and normal endometrium: Correlation with clinicopathologic parameters and biomarkers. Mod. Pathol., 19, 1593-1605 (2006).
40. Torres-Arzayus MI, Zhao J, Bronson R, Brown M. Estrogen-dependent and estrogen-independent mechanisms contribute to AIB1-mediated tumor formation. Cancer Res., 70, 4102-4111 (2010).
41. Sun HQ, Yamamoto M, Mejillano M, Yin HL. Gelsolin, a multifunctional actin regulatory protein. J. Biol. Chem., 274, 33179-33182 (1999).
42. Fujita H, Allen PG, Janmey PA, Azuma T, Kwiatkowski DJ, Stossel TP, Kuzumaki N. Induction of apoptosis by gelsolin truncates. Ann. N. Y. Acad. Sci., 886, 217-220 (1999).
43. Silacci P, Mazzolai L, Gauci C, Stergiopulos N, Yin HL, Hayoz D. Gelsolin superfamily proteins: Key regulators of cellular functions. Cell. Mol. Life Sci., 61, 2614-2623 (2004).
44. Francois M, Harvey NL, Hogan BM. The transcriptional control of lymphatic vascular development. Physiology (Bethesda), 26, 146-155 (2011).
45. Moras D, Gronemeyer H. The nuclear receptor ligand-binding domain: Structure and function. Curr. Opin. Cell Biol., 10, 384-391 (1998).
46. Palvimo JJ, Kallio PJ, Ikonen T, Mehto M, Jänne OA. Dominant negative regulation of trans-activation by the rat androgen receptor: Roles of the N-terminal domain and heterodimer formation. Mol. Endocrinol., 7, 1399-1407 (1993).
47. Moilanen A, Rouleau N, Ikonen T, Palvimo JJ, Jänne OA. The presence of a transcription activation function in the hormone-binding domain of androgen receptor is revealed by studies in yeast cells. FEBS Lett., 412, 355-358 (1997).
48. Heery DM, Kalkhoven E, Hoare S, Parker MG. A signature motif in transcriptional co-activators mediates binding to nuclear receptors. Nature, 387, 733-736 (1997).
49. Heinlein CA, Chang C. Androgen receptor (AR) coregulators: An overview. Endocr. Rev., 23, 175-200 (2002).
50. Bevan CL, Hoare S, Claessens F, Heery DM, Parker MG. The AF1 and AF2 domains of the androgen receptor interact with distinct regions of SRC1. Mol. Cell. Biol., 19, 8383-8392 (1999).
51. Alen P, Claessens F, Verhoeven G, Rombauts W, Peeters B. The androgen receptor amino-terminal domain plays a key role in p160 coactivator-stimulated gene transcription. Mol. Cell. Biol., 19, 6085-6097 (1999).
52. Berry M, Metzger D, Chambon P. Role of the two activating domains of the oestrogen receptor in the cell-type and promotercontext dependent agonistic activity of the anti-oestrogen 4-hydroxytamoxifen. EMBO J., 9, 2811-2818 (1990).
53. Metzger D, Losson R, Bornert JM, Lemoine Y, Chambon P. Promoter specificity of the two transcriptional activation functions of the human oestrogen receptor in yeast. Nucleic Acids Res., 20, 2813-2817 (1992).
54. Kumar V, Green S, Stack G, Berry M, Jin JR, Chambon P. Functional domains of the human estrogen receptor. Cell, 51, 941-951 (1987).
55. Kobayashi Y, Kitamoto T, Masuhiro Y, Watanabe M, Kase T, Metzger D, Yanagisawa J, Kato S. p300 mediates functional synergism between AF-1 and AF-2 of estrogen receptor a and β by interacting directly with the N-terminal A/B domains. J. Biol. Chem., 275, 15645-15651 (2000).