Korean J Androl. 2012 Apr;30(1):1-12. Korean.
Published online Apr 30, 2012.
Copyright © Korean Society for Sexual Medicine and Andrology
Review

5α-Reductase

Jung-Se Park,1 Min Chul Cho,2 and Jae-Seung Paick3
    • 1Park's Urologic Clinic, Changwon, Korea.
    • 2Department of Urology, Dongguk University College of Medicine, Seoul, Korea.
    • 3Department of Urology, Seoul National University College of Medicine, Seoul, Korea.
Received April 03, 2012; Revised April 16, 2012; Accepted April 19, 2012.

Abstract

Androgen acts via the androgen receptor and can play a critical role in the development and growth of the prostate and the pathophysiology of prostatic diseases. Testosterone is the most abundant circulating androgen and is converted to dihydrotestosterone (DHT), a more potent androgen, by steroid 5α-reductase. There are two 5α-reductase isoenzymes, type 1 and type 2, in humans and animals. Type 2 5α-reductase predominates in the prostate. While deficiency of type 2 5α-reductase causes male pseudohermaphroditism, increased DHT has been implicated in benign prostatic hyperplasia and prostate cancer. The aim of this article is to highlight the significance of 5α-reductase in the development and growth of the prostate and pathogenesis of prostatic diseases.

Keywords
5alpha-reductase; Sexual development; Prostate; Prostatic hyperplasia; Prostate neoplasms

Tables

Table 1
Comparison of the two human 5α-reductase isoenzymes

References

    1. Zhu YS, Katz MD, Imperato-McGinley J. Natural potent androgens: lessons from human genetic models. Baillieres Clin Endocrinol Metab 1998;12:83–113.
    1. Veltri R, Rodriguez R. Molecular biology, endocrinology, and physiology of the prostate and seminal vesicles. In: Wein AJ, Kavoussi LR, Novick AC, Partin AW, Peters CA, editors. Campbell Walsh urology. 9th ed. Philadelphia: Saunders; 2006. pp. 2677-2726.
    1. Roehrborn CG, McConnell JD. Benign prostatic hyperplasia: etiology, pathophysiology, epidemiology, and natural history. In: Wein AJ, Kavoussi LR, Novick AC, Partin AW, Peters CA, editors. Campbell Walsh urology. 9th ed. Philadelphia: Saunders; 2006. pp. 2727-2765.
    1. Imperato-McGinley J, Gautier T, Zirinsky K, Hom T, Palomo O, Stein E, et al. Prostate visualization studies in males homozygous and heterozygous for 5 alpha-reductase deficiency. J Clin Endocrinol Metab 1992;75:1022–1026.
    1. Bartsch G, Rittmaster RS, Klocker H. Dihydrotestosterone and the concept of 5alpha-reductase inhibition in human benign prostatic hyperplasia. Eur Urol 2000;37:367–380.
    1. Russell DW, Wilson JD. Steroid 5 alpha-reductase: two genes/two enzymes. Annu Rev Biochem 1994;63:25–61.
    1. Zhu YS, Sun GH. 5α-reductase isozymes in the prostate. J Med Sci 2005;25:1–12.
    1. Mahendroo MS, Cala KM, Russell DW. 5 alpha-reduced androgens play a key role in murine parturition. Mol Endocrinol 1996;10:380–392.
    1. Wilson JD. The role of 5alpha-reduction in steroid hormone physiology. Reprod Fertil Dev 2001;13:673–678.
    1. Iehlé C, Radvanyi F, Gil Diez de Medina S, Ouafik LH, Gérard H, Chopin D, et al. Differences in steroid 5alpha-reductase iso-enzymes expression between normal and pathological human prostate tissue. J Steroid Biochem Mol Biol 1999;68:189–195.
    1. Thomas LN, Douglas RC, Vessey JP, Gupta R, Fontaine D, Norman RW, et al. 5alpha-reductase type 1 immunostaining is enhanced in some prostate cancers compared with benign prostatic hyperplasia epithelium. J Urol 2003;170:2019–2025.
    1. Habib FK, Ross M, Bayne CW, Bollina P, Grigor K, Chapman K. The loss of 5alpha-reductase type I and type II mRNA expression in metastatic prostate cancer to bone and lymph node metastasis. Clin Cancer Res 2003;9:1815–1819.
    1. Spencer JR, Torrado T, Sanchez RS, Vaughan ED Jr, Imperato-McGinley J. Effects of flutamide and finasteride on rat testicular descent. Endocrinology 1991;129:741–748.
    1. Prahalada S, Tarantal AF, Harris GS, Ellsworth KP, Clarke AP, Skiles GL, et al. Effects of finasteride, a type 2 5-alpha reductase inhibitor, on fetal development in the rhesus monkey (Macaca mulatta). Teratology 1997;55:119–131.
    1. Andriole G, Bruchovsky N, Chung LW, Matsumoto AM, Rittmaster R, Roehrborn C, et al. Dihydrotestosterone and the prostate: the scientific rationale for 5alpha-reductase inhibitors in the treatment of benign prostatic hyperplasia. J Urol 2004;172:1399–1403.
    1. Wright AS, Douglas RC, Thomas LN, Lazier CB, Rittmaster RS. Androgen-induced regrowth in the castrated rat ventral prostate: role of 5alpha-reductase. Endocrinology 1999;140:4509–4515.
    1. Park JS, Paick JS. Prostate disease and erectile dysfunction. In: Park JS, editor. Male sexual dysfunction. 2nd ed. Seoul: Koonja; 2008. pp. 581-670.
    1. Levine AC, Liu XH, Greenberg PD, Eliashvili M, Schiff JD, Aaronson SA, et al. Androgens induce the expression of vascular endothelial growth factor in human fetal prostatic fibroblasts. Endocrinology 1998;139:4672–4678.
    1. Hayek OR, Shabsigh A, Kaplan SA, Kiss AJ, Chen MW, Burchardt T, et al. Castration induces acute vasoconstriction of blood vessels in the rat prostate concomitant with a reduction of prostatic nitric oxide synthase activity. J Urol 1999;162:1527–1531.
    1. McConnell JD, Bruskewitz R, Walsh P, Andriole G, Lieber M, Holtgrewe HL, et al. Finasteride Long-Term Efficacy and Safety Study Group. The effect of finasteride on the risk of acute urinary retention and the need for surgical treatment among men with benign prostatic hyperplasia. N Engl J Med 1998;338:557–563.
    1. McConnell JD, Roehrborn CG, Bautista OM, Andriole GL Jr, Dixon CM, Kusek JW, et al. Medical Therapy of Prostatic Symptoms (MTOPS) Research Group. The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. N Engl J Med 2003;349:2387–2398.
    1. Roehrborn CG, Boyle P, Nickel JC, Hoefner K, Andriole G. ARIA3001 ARIA3002 and ARIA3003 Study Investigators. Efficacy and safety of a dual inhibitor of 5-alpha-reductase types 1 and 2 (dutasteride) in men with benign prostatic hyperplasia. Urology 2002;60:434–441.
    1. Roehrborn CG, Siami P, Barkin J, Damião R, Major-Walker K, Nandy I, et al. CombAT study group. The effects of combination therapy with dutasteride and tamsulosin on clinical outcomes in men with symptomatic benign prostatic hyperplasia: 4-year results from the CombAT study. Eur Urol 2010;57:123–131.
    1. Nickel JC, Gilling P, Tammela TL, Morrill B, Wilson TH, Rittmaster RS. Comparison of dutasteride and finasteride for treating benign prostatic hyperplasia: the Enlarged Prostate International Comparator Study (EPICS). BJU Int 2011;108:388–394.
    1. Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin 2010;60:277–300.
    1. National Cancer Center. Goyang: National Cancer Center; [cited 2012 January]. Cancer registry system in Korea [Internet].
      Arailable from: http://www.ncc.re.kr.
    1. Makridakis NM, Ross RK, Pike MC, Crocitto LE, Kolonel LN, Pearce CL, et al. Association of mis-sense substitution in SRD5A2 gene with prostate cancer in African-American and Hispanic men in Los Angeles, USA. Lancet 1999;354:975–978.
    1. Jaffe JM, Malkowicz SB, Walker AH, MacBride S, Peschel R, Tomaszewski J, et al. Association of SRD5A2 genotype and pathological characteristics of prostate tumors. Cancer Res 2000;60:1626–1630.
    1. Homma Y, Kaneko M, Kondo Y, Kawabe K, Kakizoe T. Inhibition of rat prostate carcinogenesis by a 5alpha-reductase inhibitor, FK143. J Natl Cancer Inst 1997;89:803–807.
    1. Thompson IM, Goodman PJ, Tangen CM, Lucia MS, Miller GJ, Ford LG, et al. The influence of finasteride on the development of prostate cancer. N Engl J Med 2003;349:215–224.
    1. Thompson IM, Klein EA, Lippman SM, Coltman CA, Djavan B. Prevention of prostate cancer with finasteride: US/European perspective. Eur Urol 2003;44:650–655.
    1. Thompson IM, Chi C, Ankerst DP, Goodman PJ, Tangen CM, Lippman SM, et al. Effect of finasteride on the sensitivity of PSA for detecting prostate cancer. J Natl Cancer Inst 2006;98:1128–1133.
    1. Redman MW, Tangen CM, Goodman PJ, Lucia MS, Coltman CA Jr, Thompson IM. Finasteride does not increase the risk of high-grade prostate cancer: a bias-adjusted modeling approach. Cancer Prev Res (Phila) 2008;1:174–178.
    1. Walsh PC. Urological oncology: prostate cancer. J Urol 2004;171:506–517.
    1. Zaccheo T, Giudici D, Panzeri A, di Salle E. Effect of the 5 alpha-reductase inhibitor PNU 156765, alone or in combination with flutamide, in the Dunning R3327 prostatic carcinoma model in rats. Chemotherapy 1998;44:284–292.
    1. Lazier CB, Thomas LN, Douglas RC, Vessey JP, Rittmaster RS. Dutasteride, the dual 5alpha-reductase inhibitor, inhibits androgen action and promotes cell death in the LNCaP prostate cancer cell line. Prostate 2004;58:130–144.
    1. Andriole GL, Bostwick DG, Brawley OW, Gomella LG, Marberger M, Montorsi F, et al. REDUCE study group. Effect of dutasteride on the risk of prostate cancer. N Engl J Med 2002;362:1192–1202.
    1. Hamilton RJ, Freedland SJ. 5-α reductase inhibitors and prostate cancer prevention: where do we turn now? BMC Med 2011;9:105.
    1. Theoret MR, Ning YM, Zhang JJ, Justice R, Keegan P, Pazdur R. The risks and benefits of 5α-reductase inhibitors for prostate-cancer prevention. N Engl J Med 2011;365:97–99.
    1. FDA core presentation: NDA020180/s034: Proscar (finasteride 5mg tablet). US Food and Drug Administration: December 1, 2010 Meeting of the Oncologic Drugs Advisory Committee. [cited 2012 March 27].
    1. Cai LQ, Imperato-McGinley J, Zhu YS. Regulation of prostate 5alpha-reductase-2 gene expression and prostate weight by dietary fat and caloric intake in the rat. Prostate 2006;66:738–748.
    1. Cai LQ, Cai J, Wu W, Zhu YS. 17α-Estradiol and genistein inhibit high fat diet induced prostate gene expression and prostate growth in the rat. J Urol 2011;186:1489–1496.
    1. Uemura M, Tamura K, Chung S, Honma S, Okuyama A, Nakamura Y, et al. Novel 5 alpha-steroid reductase (SRD5A3, type-3) is overexpressed in hormone-refractory prostate cancer. Cancer Sci 2008;99:81–86.

Metrics
Share
Tables

1 / 1

PERMALINK