A Multiscale, Mechanism-Driven, Dynamic Model for the Effects of 5α-Reductase Inhibition on Prostate Maintenance

PLoS ONE

Volumn 7, Issue 9, 2012, Pages

  Zager, Michael G ^a   Barton, Hugh A ^a  

^a PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANDROGEN; ANDROSTANOLONE; DUTASTERIDE; FINASTERIDE; ISOENZYME; STEROID 5ALPHA REDUCTASE; TESTOSTERONE;

ADULT ANIMAL; APOPTOSIS; ARTICLE; BINDING AFFINITY; CELL PROLIFERATION; DRUG DEVELOPMENT; DRUG INDICATION; ENZYME INHIBITION; EXPERIMENTAL RAT; HORMONAL REGULATION; HORMONE METABOLISM; MALE; MATHEMATICAL MODEL; NONHUMAN; ORGAN SIZE; PROSTATE CANCER; PROSTATE DISEASE; PROSTATE FLUID; PROSTATE HYPERTROPHY; PROSTATE SIZE; PROSTATE VENTRAL LOBE; PROTEIN EXPRESSION; RAT;

5-ALPHA REDUCTASE INHIBITORS; ANIMALS; CALIBRATION; CHOLESTENONE 5 ALPHA-REDUCTASE; DIHYDROTESTOSTERONE; DOSE-RESPONSE RELATIONSHIP, DRUG; FINASTERIDE; GENE EXPRESSION REGULATION; HUMANS; KINETICS; LIVER; MALE; MODELS, BIOLOGICAL; ORGAN SIZE; PROSTATE; RATS; TESTOSTERONE;

RATTUS;

EID: 84866104463     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0044359     Document Type: Article

References (54)

1. Kholodenko B, Yaffe MB, Kolch W, (2012) Computational approaches for analyzing information flow in biological networks. Sci Signal 5: re1.
2. Hunter PJ, Borg TK, (2003) Integration from proteins to organs: the Physiome Project. Nat Rev Mol Cell Biol 4: 237-243.
3. Westerhoff HV, Palsson BO, (2004) The evolution of molecular biology into systems biology. Nat Biotechnol 22: 1249-1252.
4. Clark LH, Schlosser PM, Selgrade JF, (2003) Multiple stable periodic solutions in a model for hormonal control of the menstrual cycle. Bull Math Biol 65: 157-173.
5. Selgrade JF, Harris LA, Pasteur RD, (2009) A model for hormonal control of the menstrual cycle: structural consistency but sensitivity with regard to data. J Theor Biol 260: 572-580.
6. Pozzi P, Bendotti C, Simeoni S, Piccioni F, Guerini V, et al. (2003) Androgen 5-alpha-reductase type 2 is highly expressed and active in rat spinal cord motor neurones. J Neuroendocrinol 15: 882-887.
7. Torres JM, Ortega E, (2003) Precise quantitation of 5alpha-reductase type 1 mRNA by RT-PCR in rat liver and its positive regulation by testosterone and dihydrotestosterone. Biochem Biophys Res Commun 308: 469-473.
8. Orlowski J, Bird CE, Clark AF, (1988) Androgen metabolism and regulation of rat ventral prostate growth and acid phosphatase during sexual maturation. J Endocrinol 116: 81-90.
9. Grino PB, Griffin JE, Wilson JD, (1990) Testosterone at high concentrations interacts with the human androgen receptor similarly to dihydrotestosterone. Endocrinology 126: 1165-1172.
10. Gubbay J, Doyle JP, Skinner M, Heintz N, (1998) Changing patterns of gene expression identify multiple steps during regression of rat prostate in vivo. Endocrinology 139: 2935-2943.
11. Isaacs JT, (1984) Antagonistic effect of androgen on prostatic cell death. Prostate 5: 545-557.
12. Nnane IP, Kato K, Liu Y, Lu Q, Wang X, et al. (1998) Effects of some novel inhibitors of C17,20-lyase and 5alpha-reductase in vitro and in vivo and their potential role in the treatment of prostate cancer. Cancer Res 58: 3826-3832.
13. Prins GS, (1989) Differential regulation of androgen receptors in the separate rat prostate lobes: androgen independent expression in the lateral lobe. J Steroid Biochem 33: 319-326.
14. Suzuki K, Ito K, Kurokawa K, Suzuki T, Shimizu N, et al. (1997) Expression and degradation of rat androgen receptor following castration, testosterone replacement and antiandrogens administration: analysis by Western blot and immunohistochemistry. Tohoku J Exp Med 183: 159-172.
15. George FW, Russell DW, Wilson JD, (1991) Feed-forward control of prostate growth: dihydrotestosterone induces expression of its own biosynthetic enzyme, steroid 5 alpha-reductase. Proc Natl Acad Sci U S A 88: 8044-8047.
16. Berman DM, Russell DW, (1993) Cell-type-specific expression of rat steroid 5 alpha-reductase isozymes. Proc Natl Acad Sci U S A 90: 9359-9363.
17. Frye SV, Haffner CD, Maloney PR, Hiner RN, Dorsey GF, et al. (1995) Structure-activity relationships for inhibition of type 1 and 2 human 5 alpha-reductase and human adrenal 3 beta-hydroxy-delta 5-steroid dehydrogenase/3-keto-delta 5-steroid isomerase by 6-azaandrost-4-en-3-ones: optimization of the C17 substituent. J Med Chem 38: 2621-2627.
18. Habib FK, Ross M, Bayne CW, Grigor K, Buck AC, et al. (1998) The localisation and expression of 5 alpha-reductase types I and II mRNAs in human hyperplastic prostate and in prostate primary cultures. J Endocrinol 156: 509-517.
19. Normington K, Russell DW, (1992) Tissue distribution and kinetic characteristics of rat steroid 5 alpha-reductase isozymes. Evidence for distinct physiological functions. J Biol Chem 267: 19548-19554.
20. Thomas LN, Douglas RC, Lazier CB, Gupta R, Norman RW, et al. (2008) Levels of 5alpha-reductase type 1 and type 2 are increased in localized high grade compared to low grade prostate cancer. J Urol 179: 147-151.
21. Tindall DJ, Rittmaster RS, (2008) The rationale for inhibiting 5alpha-reductase isoenzymes in the prevention and treatment of prostate cancer. J Urol 179: 1235-1242.
22. Frye SV, Bramson HN, Hermann DJ, Lee FW, Sinhababu AK, et al. (1998) Discovery and development of GG745, a potent inhibitor of both isozymes of 5 alpha-reductase. Pharm Biotechnol 11: 393-422.
23. Vermeulen A, Giagulli VA, De Schepper P, Buntinx A, (1991) Hormonal effects of a 5 alpha-reductase inhibitor (finasteride) on hormonal levels in normal men and in patients with benign prostatic hyperplasia. Eur Urol 20 (Suppl 1):: 82-86.
24. Azzolina B, Ellsworth K, Andersson S, Geissler W, Bull HG, et al. (1997) Inhibition of rat alpha-reductases by finasteride: evidence for isozyme differences in the mechanism of inhibition. J Steroid Biochem Mol Biol 61: 55-64.
25. Gisleskog PO, Hermann D, Hammarlund-Udenaes M, Karlsson MO, (1999) The pharmacokinetic modelling of GI198745 (dutasteride), a compound with parallel linear and nonlinear elimination. Br J Clin Pharmacol 47: 53-58.
26. Stuart JD, Lee FW, Simpson Noel D, Kadwell SH, Overton LK, et al. (2001) Pharmacokinetic parameters and mechanisms of inhibition of rat type 1 and 2 steroid 5alpha-reductases: determinants for different in vivo activities of GI198745 and finasteride in the rat. Biochem Pharmacol 62: 933-942.
27. Cohen YC, Liu KS, Heyden NL, Carides AD, Anderson KM, et al. (2007) Detection bias due to the effect of finasteride on prostate volume: a modeling approach for analysis of the Prostate Cancer Prevention Trial. J Natl Cancer Inst 99: 1366-1374.
28. Kaplan SA, Roehrborn CG, Meehan AG, Liu KS, Carides AD, et al. (2009) PCPT: Evidence that finasteride reduces risk of most frequently detected intermediate- and high-grade (Gleason score 6 and 7) cancer. Urology 73: 935-939.
29. Pinsky P, Parnes H, Ford L, (2008) Estimating rates of true high-grade disease in the prostate cancer prevention trial. Cancer Prev Res (Phila) 1: 182-186.
30. Thompson IM, Goodman PJ, Tangen CM, Lucia MS, Miller GJ, et al. (2003) The influence of finasteride on the development of prostate cancer. N Engl J Med 349: 215-224.
31. Thompson IM, Tangen CM, Parnes HL, Lippman SM, Coltman CA Jr, (2008) Does the level of prostate cancer risk affect cancer prevention with finasteride? Urology 71: 854-857.
32. Xu Y, Dalrymple SL, Becker RE, Denmeade SR, Isaacs JT, (2006) Pharmacologic basis for the enhanced efficacy of dutasteride against prostatic cancers. Clin Cancer Res 12: 4072-4079.
33. Scher HI, Sawyers CL, (2005) Biology of progressive, castration-resistant prostate cancer: directed therapies targeting the androgen-receptor signaling axis. J Clin Oncol 23: 8253-8261.
34. Eikenberry SE, Nagy JD, Kuang Y, (2010) The evolutionary impact of androgen levels on prostate cancer in a multi-scale mathematical model. Biol Direct 5: 24.
35. Suzuki R, Satoh H, Ohtani H, Hori S, Sawada Y, (2010) Saturable binding of finasteride to steroid 5alpha-reductase as determinant of nonlinear pharmacokinetics. Drug Metab Pharmacokinet 25: 208-213.
36. Potter LK, Zager MG, Barton HA, (2006) Mathematical model for the androgenic regulation of the prostate in intact and castrated adult male rats. Am J Physiol Endocrinol Metab 291: E952-964.
37. Tenniswood M, Abrahams P, Winterton V, Bird CE, Clark AF, (1982) Binding of testosterone, 5 alpha-dihydrotestosterone and 5 alpha-androstane (3 alpha- and 3 beta-), 17 beta-diols to serum proteins in the rat. J Steroid Biochem 16: 617-620.
38. Turner TT, Nguyen QT, (2002) Response of the adult prostate to prepubertal and postpubertal obstruction of the vas deferens in the rat. Urology 60: 186-190.
39. Bull HG, Garcia-Calvo M, Andersson S, Baginsky WF, Chan HK, (1996) Mechanism-Based Inhibition of Human Steroid 5R-Reductase by Finasteride: Enzyme-Catalyzed Formation of NADP-Dihydrofinasteride, a Potent Bisubstrate Analog Inhibitor. J Am Chem Soc 118: 2359-2365.
40. Segal IH (1975) Enzyme kinetics: behavior and analysis of rapid equilibrium and steady-state enzyme systems. New York: Wiley-Interscience. 957 p.
41. Sudduth SL, Koronkowski MJ (1993) Finasteride: the first 5 alpha-reductase inhibitor. Pharmacotherapy 13: 309-325; discussion 325-309.
42. Rittmaster RS, Manning AP, Wright AS, Thomas LN, Whitefield S, et al. (1995) Evidence for atrophy and apoptosis in the ventral prostate of rats given the 5 alpha-reductase inhibitor finasteride. Endocrinology 136: 741-748.
43. Gregory CW, Johnson RT Jr, Mohler JL, French FS, Wilson EM, (2001) Androgen receptor stabilization in recurrent prostate cancer is associated with hypersensitivity to low androgen. Cancer Res 61: 2892-2898.
44. Lee E, Salic A, Kruger R, Heinrich R, Kirschner MW, (2003) The roles of APC and Axin derived from experimental and theoretical analysis of the Wnt pathway. PLoS Biol 1: E10.
45. Wright AS, Thomas LN, Douglas RC, Lazier CB, Rittmaster RS, (1996) Relative potency of testosterone and dihydrotestosterone in preventing atrophy and apoptosis in the prostate of the castrated rat. J Clin Invest 98: 2558-2563.
46. Barton HA, Andersen ME, (1998) A model for pharmacokinetics and physiological feedback among hormones of the testicular-pituitary axis in adult male rats: a framework for evaluating effects of endocrine active compounds. Toxicol Sci 45: 174-187.
47. Attard G, Cooper CS, de Bono JS, (2009) Steroid hormone receptors in prostate cancer: a hard habit to break? Cancer Cell 16: 458-462.
48. Burd CJ, Petre CE, Morey LM, Wang Y, Revelo MP, et al. (2006) Cyclin D1b variant influences prostate cancer growth through aberrant androgen receptor regulation. Proc Natl Acad Sci U S A 103: 2190-2195.
49. Gregory CW, He B, Johnson RT, Ford OH, Mohler JL, et al. (2001) A mechanism for androgen receptor-mediated prostate cancer recurrence after androgen deprivation therapy. Cancer Res 61: 4315-4319.
50. Petre-Draviam CE, Cook SL, Burd CJ, Marshall TW, Wetherill YB, et al. (2003) Specificity of cyclin D1 for androgen receptor regulation. Cancer Res 63: 4903-4913.
51. Sadar MD, Hussain M, Bruchovsky N, (1999) Prostate cancer: molecular biology of early progression to androgen independence. Endocr Relat Cancer 6: 487-502.
52. Jain HV, Clinton SK, Bhinder A, Friedman A, (2011) Mathematical modeling of prostate cancer progression in response to androgen ablation therapy. Proc Natl Acad Sci U S A 108: 19701-19706.
53. Heinrich R, Schuster S (1996) The regulation of cellular systems. New York City: Chapman and Hall. 372 p.
54. Fell D (1997) Understanding the control of metabolism. London: Portland Press. 300 p.