臨床泌尿器科61巻2号

2007年02月発行

セミナー 下部尿路症状（LUTS）診療の最前線・4

前立腺肥大症に関する最近の話題

著者： 小島祥敬¹ 窪田泰江¹ 佐々木昌一¹ 林祐太郎¹ 郡健二郎¹

所属機関： ¹名古屋市立大学大学院医学研究科腎・泌尿器科学分野

ページ範囲：P.139 - P.145

文献概要

要約：前立腺肥大症の概念は，下部尿路症状（lower urinary tract symptoms：LUTS），前立腺の腫大（benign prostatic enlargement：BPE），膀胱排出路の閉塞（bladder outlet obstruction：BOO）という3つの要素で構成される。日常診療においてよく遭遇する疾患であるが，その病態については意外なほどよくわかっていないのが現状である。病態を明らかにするうえでは，排尿にかかわる生理学的・薬理学的理解と細胞増殖にかかわる分子生物学的理解が必要となる。本稿では，前立腺平滑筋のトーヌス維持にかかわるα₁受容体サブタイプに関する最近の知見と前立腺間質増殖に関与する因子についての最近の話題について中心に概説した。

参考文献

1）Roehrborn CG：Benign prostatic hyperplasia；An Overview. Rev Urol 7：3-14, 2005

2）Roehrborn C and McConnell J：Etiology, pathphysiology, epidemiology and natural history of benign prostatic hyperplasia. In：Campbell's Urology. 8th ed. edited by Walsh P, Retik A, Vaughan E and Wein A. Philadelphia, Saunders, pp1297-1336, 2002

3）Girman CJ, Panser LA, Chute CG, et al：Natural history of prostatism：urinary flow rates in a community-based study. J Urol 150：887-892, 1993

4）Jacobsen SJ, Girman CJ and Lieber MM：Natural history of benign prostatic hyperplasia. Urology 58：5-16, 2001

5）Barry MJ, Cockett AT, Holtgrewe HL, et al：Relationship of symptoms of prostatism to commonly used physiological and anatomical measures of the severity of benign prostatic hyperplasia. J Urol 150：351-358, 1993

6）Shapiro E, Hartanto V and Lepor H：Anti-desmin vs. anti-actin for quantifying the area density of prostate smooth muscle. Prostate 20：259-267, 1992

7）Shapiro E, Becich MJ, Hartanto V, et al：The relative proportion of stromal and epithelial hyperplasia is related to the development of symptomatic benign prostate hyperplasia. J Urol 147：1293-1297, 1992

8）Spitsbergen JM, Clemow DB, McCarty R, et al：Neurally mediated hyperactive voiding in spontaneously hypertensive rats. Brain Res 790：151-159, 1998

9）Kojima Y, Sasaki S, Shinoura H, et al：Quantification of alpha1-adrenoceptor subtypes by real-time RT-PCR and correlation with age and prostate volume in benign prostatic hyperplasia patients. Prostate 66：761-767, 2006

10）Hieble JP, Bylund DB, Clarke DE, et al：International Union of Pharmacology. X. Recommendation for nomenclature of alpha 1-adrenoceptors：consensus update. Pharmacol Rev 47：267-270, 1995

11）Price DT, Lefkowitz RJ, Caron MG, et al：Localization of mRNA for three distinct alpha 1-adrenergic receptor subtypes in human tissues：implications for human alpha-adrenergic physiology. Mol Pharmacol 45：171-175, 1994

12）Nasu K, Moriyama N, Kawabe K, et al：Quantification and distribution of alpha 1-adrenoceptor subtype mRNAs in human prostate：comparison of benign hypertrophied tissue and non-hypertrophied tissue. Br J Pharmacol 119：797-803, 1996

13）Price DT, Schwinn DA, Lomasney JW, et al：Identification, quantification, and localization of mRNA for three distinct alpha 1 adrenergic receptor subtypes in human prostate. J Urol 150：546-551, 1993

14）Ikemoto I, Kiyota H, Ohishi Y, et al：Usefulness of tamsulosin hydrochloride and naftopidil in patients with urinary disturbances caused by benign prostatic hyperplasia：a comparative, randomized, two-drug crossover study. Int J Urol 10：587-594, 2003

15）Takei R, Ikegaki I, Shibata K, et al：Naftopidil, a novel alpha1-adrenoceptor antagonist, displays selective inhibition of canine prostatic pressure and high affinity binding to cloned human alpha1-adrenoceptors. Jpn J Pharmacol 79：447-454, 1999

16）Blue D, Alto P, Zinner N, et al：RO700004, a selective α1 A-adrenoceptor antagonist, does not improve lower urinary tract symptoms in men with benign prostatic hyperplasia. J Urol 167（supplement）：265, 2002

17）Evans WE and McLeod HL：Pharmacogenomics-drug disposition, drug targets, and side effects. N Engl J Med 348：538-549, 2003

18）Kojima Y, Sasaki S, Shinoura H, et al：Correlation between alpha1-adprenoceptor subtype mRNA expression level and efficacy of naftopidil for BPH patients. Neurourol Urodyn 23：467-468, 2004

19）Berthaut I, Mestayer C, Portois MC, et al：Pharmacological and molecular evidence for the expression of the two steroid 5 alpha-reductase isozymes in normal and hyperplastic human prostatic cells in culture. Prostate 32：155-163, 1997

20）Mestayer C, Blanchere M, Jaubert F, et al：Expression of androgen receptor coactivators in normal and cancer prostate tissues and cultured cell lines. Prostate 56：192-200, 2003

21）Agoulnik IU, Krause WC, Bingman WE 3rd, et al：Repressors of androgen and progesterone receptor action. J Biol Chem 278：31136-31148, 2003

22）Ropiquet F, Giri D, Lamb DJ, et al：FGF7 and FGF2 are increased in benign prostatic hyperplasia and are associated with increased proliferation. J Urol 162：595-599, 1999

23）Kyprianou N, Tu H and Jacobs SC：Apoptotic versus proliferative activities in human benign prostatic hyperplasia. Hum Pathol 27：668-675, 1996

24）Giri D and Ittmann M：Interleukin-1 alpha is a paracrine inducer of FGF7, a key epithelial growth factor in benign prostatic hyperplasia. Am J Pathol 157：249-255, 2000

25）Levitt JM, Song W, Guariguata L, et al：Up-regulation of a family of interferon-inducible inflammatory chemokines in benign prostatic hyperplasia. J Urol 175：468, 2006

26）Kramer G, Steiner GE, Handisurya A, et al：Increased expression of lymphocyte-derived cytokines in benign hyperplastic prostate tissue, identification of the producing cell types, and effect of differentially expressed cytokines on stromal cell proliferation. Prostate 52：43-58, 2002

27）Kramer G and Marberger M：Could inflammation be a key component in the progression of benign prostatic hyperplasia. Curr Opin Urol 16：25-29, 2006

28）Fromont G, Chene L, Latil A, et al：Molecular profiling of benign prostatic hyperplasia using a large scale real-time reverse transcriptase-polymerase chain reaction approach. J Urol 172：1382-1385, 2004

29）Kubota Y, Kajioka S, Biers SM, et al：Investigation of the effect of the c-kit inhibitor Glivec on isolated guinea-pig detrusor preparations. Auton Neurosci 30；115：64-73, 2004

30）Kubota Y, Biers SM, Kohri K, et al：Effects of imatinib mesylate（Glivec）as a c-kit tyrosine kinase inhibitor in the guinea-pig urinary bladder. Neurourol Urodyn 25：205-210, 2006

31）Van der Aa F, Roskams T, Blyweert W, et al：Interstitial cells in the human prostate：a new therapeutic target? Prostate 56：250-255, 2003

32）Lee KL and Peehl DM：Molecular and cellular pathogenesis of benign prostatic hyperplasia. J Urol 172：1784-1791, 2004

33）Prakash K, Pirozzi G, Elashoff M, et al：Symptomatic and asymptomatic benign prostatic hyperplasia：molecular differentiation by using micro-arrays. Proc Natl Acad Sci USA 99：7598-7603, 2002

34）Cannon GW and Getzenberg RH：A serum-based assay for JM-27 can identifynmen with symptomatic benign prostatic hyperplasia. J Urol 175：436, 2006

35）Walden PD, Lefkowitz GK, Ficazzola M, et al：Identification of genes associated with stromal hyperplasia and glandular atrophy of the prostate by mRNA differential display. Exp Cell Res 245：19-26, 1998