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The role of the androgen receptor in prostate development and benign prostatic hyperplasia: A review |
Renee E. Vickmana,Omar E. Francoa,Daniel C. Molineb,Donald J. Vander Griendb,Praveen Thumbikatc,Simon W. Haywarda,*()
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a Department of Surgery, NorthShore University HealthSystem, Evanston, IL, USA b Department of Pathology, University of Illinois at Chicago, Chicago, IL, USA c Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA |
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Abstract Benign prostatic hyperplasia (BPH) is a benign enlargement of the prostate in which incidence increases linearly with age, beginning at about 50 years old. BPH is a significant source of morbidity in aging men by causing lower urinary tract symptoms and acute urinary retention. Unfortunately, the etiology of BPH incidence and progression is not clear. This review highlights the role of the androgen receptor (AR) in prostate development and the evidence for its involvement in BPH. The AR is essential for normal prostate development, and individuals with defective AR signaling, such as after castration, do not experience prostate enlargement with age. Furthermore, decreasing dihydrotestosterone availability through therapeutic targeting with 5α-reductase inhibitors diminishes AR activity and results in reduced prostate size and symptoms in some BPH patients. While there is some evidence that AR expression is elevated in certain cellular compartments, how exactly AR is involved in BPH progression has yet to be elucidated. It is possible that AR signaling within stromal cells alters intercellular signaling and a “reawakening” of the embryonic mesenchyme, loss of epithelial AR leads to changes in paracrine signaling interactions, and/or chronic inflammation aids in stromal or epithelial proliferation evident in BPH. Unfortunately, a subset of patients fails to respond to current medical approaches, forcing surgical treatment even though age or associated co-morbidities make surgery less attractive. Fundamentally, new therapeutic approaches to treat BPH are not currently forthcoming, so a more complete molecular understanding of BPH etiology is necessary to identify new treatment options.
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Received: 25 April 2019
Available online: 20 July 2020
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Corresponding Authors:
Simon W. Hayward
E-mail: shayward@northshore.org
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Benign prostatic hyperplasia (BPH) in human prostate tissue. (A) Diagrams representing anatomical features of normal human prostate and BPH. BPH originates within the preprostatic region, containing the transition zone (TZ) and periurethral glands. A dashed line through the BPH diagram represents an approximate cross-sectional location of a whole-mount pathological view of BPH, as in (B) and (C). Human prostate cut along the transverse plan to observe a gross view (B) or whole mount H&E section (C). TZ and peripheral zone (PZ) are labeled and BPH nodules are indicated by black arrows. Modified from Aaron et al. [8].
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Androgen receptor (AR) expression in prostatic cell types during development. Prostatic development is initiated with development of a urogenital sinus (UGS), followed by extension of prostatic buds forming an immature prostate gland. The adult prostate gland contains fully differentiated stromal and epithelial compartments which form a mature and functional organ. AR is initially expressed in just a proportion of the urogenital sinus mesenchyme (UGM). Epithelial cells gain AR expression throughout development. While only a subset of stromal cells (e.g. fibroblasts and smooth muscle cells) maintain AR expression in the adult prostate, virtually all luminal epithelial cells express AR.
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General protein structures of androgen receptor (AR) and AR-V7. Full-length AR contains functional domains: NTD, N terminal domain; DBD, DNA-binding domain; H, hinge region; LBD, ligand-binding domain. General locations of the nuclear localization signal (NLS) and nuclear export signal (NES) are indicated, along with regions of transcriptional activation function (AF)-1 and AF-2 binding sites. AR-V7 contains the NTD and DBD, but alternative splicing of the gene truncates the protein leaving only cryptic exon 3 (CE3) at the C-terminus. Numbers flanking domains indicate the approximate amino acid at that location.
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Summary of alterations in BPH. The normal adult prostate has low immune cell infiltration, basal AR expression, and basal levels of NF-κB activity, allowing for steady-state cell death/proliferation rates and maintenance of tissue homeostasis. In a prostate with BPH, there is increased collagen deposition and infiltration of inflammatory mediators, such as T cells and macrophages, resulting in a chronic inflammatory status within the prostate. Elevated inflammation results in NF-κB activation, which has been demonstrated to stimulate expression of SRD5A2, AR, and AR-V7. Inflammation, NF-κB activity, or AR could each be involved in the development of hyperplasia in epithelial or stromal cells observed in BPH nodules. AR, androgen receptor; BPH, benign prostatic hyperplasia; SRD5A2, 5α-reductase 2.
|
[1] |
Lowsley OS. The development of the human prostate gland with reference to the development of other structures at the neck of the urinary bladder. Am J Anat 1912; 13:299-349.
|
[2] |
Cunha GR, Vezina CM, Isaacson D, Ricke WA, Timms BG, Cao M, et al. Development of the human prostate. Differentiation 2018; 103:24-45.
|
[3] |
McNeal JE. Anatomy of the prostate and morphogenesis of BPH. Prog Clin Biol Res 1984; 145:27-53.
|
[4] |
McNeal JE. The zonal anatomy of the prostate. Prostate 1981; 2:35-49.
|
[5] |
Leach DA, Need EF, Toivanen R, Trotta AP, Palethorpe HM, Tamblyn DJ, et al. Stromal androgen receptor regulates the composition of the microenvironment to influence prostate cancer outcome. Oncotarget 2015; 6:16135-50.
|
[6] |
Lilja H, Abrahamsson PA. Three predominant proteins secreted by the human prostate gland. Prostate 1988; 12:29-38.
|
[7] |
Isaacs JT, Coffey DS. Etiology and disease process of benign prostatic hyperplasia. Prostate Suppl 1989; 2:33-50.
|
[8] |
Aaron L, Franco OE, Hayward SW. Review of prostate anatomy and embryology and the etiology of benign prostatic hyperplasia. Urol Clin N Am 2016; 43:279-88.
|
[9] |
Mobley D, Feibus A, Baum N. Benign prostatic hyperplasia and urinary symptoms: evaluation and treatment. Postgrad Med 2015; 127:301-7.
|
[10] |
Le Duc IE. The anatomy of the prostate and the pathology of early benign hypertrophy. J Urol 1939; 42:1217-41.
|
[11] |
Izumi K, Mizokami A, Lin WJ, Lai KP, Chang C. Androgen receptor roles in the development of benign prostate hyperplasia. Am J Pathol 2013; 182:1942-9.
|
[12] |
Fusco F, Palmieri A, Ficarra V, Giannarini G, Novara G, Longo N, et al. Alpha1-blockers improve benign prostatic obstruction in men with lower urinary tract symptoms: a systematic review and meta-analysis of urodynamic studies. Eur Urol 2016; 69:1091-101.
|
[13] |
Rodriguez-Nieves JA, Macoska JA. Prostatic fibrosis, lower urinary tract symptoms, and BPH. Nat Rev Urol 2013; 10:546-50.
|
[14] |
Strand DW, Costa DN, Francis F, Ricke WA, Roehrborn CG. Targeting phenotypic heterogeneity in benign prostatic hyperplasia. Differentiation 2017; 96:49-61.
|
[15] |
Berry SJ, Coffey DS, Walsh PC, Ewing LL. The development of human benign prostatic hyperplasia with age. J Urol 1984; 132:474-9.
|
[16] |
Gao N, Zhang J, Rao MA, Case TC, Mirosevich J, Wang Y, et al. The role of hepatocyte nuclear factor-3 alpha (Forkhead Box A1) and androgen receptor in transcriptional regulation of prostatic genes. Mol Endocrinol 2003; 17:1484-507.
|
[17] |
Leach DA, Panagopoulos V, Nash C, Bevan C, Thomson AA, Selth LA, et al. Cell-lineage specificity and role of AP-1 in the prostate fibroblast androgen receptor cistrome. Mol Cell Endocrinol 2017; 439:261-72.
|
[18] |
Cooke PS, Young P, Cunha GR. Androgen receptor expression in developing male reproductive organs. Endocrinology 1991; 128:2867-73.
|
[19] |
Mirosevich J, Gao N, Matusik RJ. Expression of Foxa transcription factors in the developing and adult murine prostate. Prostate 2005; 62:339-52.
|
[20] |
Cunha GR, Donjacour AA, Cooke PS, Mee S, Bigsby RM, Higgins SJ, et al. The endocrinology and developmental biology of the prostate. Endocr Rev 1987; 8:338-62.
|
[21] |
Cunha GR, Fujii H, Neubauer BL, Shannon JM, Sawyer L, Reese BA, et al. Epithelial-mesenchymal interactions in prostatic development. I. morphological observations of prostatic induction by urogenital sinus mesenchyme in epithelium of the adult rodent urinary bladder. J Cell Biol 1983; 96:1662-70.
|
[22] |
Cunha GR. The dual origin of vaginal epithelium. Am J Anat 1975; 143:387-92.
|
[23] |
Cunha GR, Chung LW. Stromal-epithelial interactions-I. Induction of prostatic phenotype in urothelium of testicular feminized (Tfm/y) mice. J Steroid Biochem 1981; 14:1317-24.
|
[24] |
Donjacour AA, Cunha GR. Assessment of prostatic protein secretion in tissue recombinants made of urogenital sinus mesenchyme and urothelium from normal or androgeninsensitive mice. Endocrinology 1993; 132:2342-420.
|
[25] |
Kemppainen JA, Lane MV, Sar M, Wilson EM. Androgen receptor phosphorylation, turnover, nuclear transport, and transcriptional activation. Specificity for steroids and antihormones. J Biol Chem 1992; 267:968-74.
|
[26] |
Gao W, Bohl CE, Dalton JT. Chemistry and structural biology of androgen receptor. Chem Rev 2005; 105:3352-70.
|
[27] |
Imperato-McGinley JGL, Gautier T, Peterson RE. Steroid 5alpha-reductase deficiency in man: an inherited form of male pseudohermaphroditism. Science 1974; 186:1213-5.
|
[28] |
Umesono K, Evans RM. Determinants of target gene speci- ficity for steroid/thyroid hormone receptors. Cell 1989; 57:1139-46.
|
[29] |
Cutress ML, Whitaker HC, Mills IG, Stewart M, Neal DE. Structural basis for the nuclear import of the human androgen receptor. J Cell Sci 2008; 121:957-8.
|
[30] |
Lonergan PE, Tindall DJ. Androgen receptor signaling in prostate cancer development and progression. J Carcinog 2011; 10:20. https://doi.org/10.4103/1477-3163.83937.
doi: 10.4103/1477-3163.83937
pmid: 21886458
|
[31] |
Lallous N, Dalal K, Cherkasov A, Rennie PS. Targeting alternative sites on the androgen receptor to treat castrationresistant prostate cancer. Int J Mol Sci 2013; 14:12496-519.
|
[32] |
Lu J, Van der Steen T, Tindall DJ. Are androgen receptor variants a substitute for the full-length receptor? Nat Rev Urol 2015; 12:137-44.
|
[33] |
Dehm SM, Tindall DJ. Alternatively spliced androgen receptor variants. Endocr Relat Cancer 2011; 18:R183-96.
|
[34] |
Ahrens-Fath I, Politz O, Geserick C, Haendler B. Androgen receptor function is modulated by the tissue-specific AR45 variant. FEBS J 2005; 272:74-84.
|
[35] |
Hu R, Dunn TA, Wei S, Isharwal S, Veltri RW, Humphreys E, et al. Ligand-independent androgen receptor variants derived from splicing of cryptic exons signify hormonerefractory prostate cancer. Cancer Res 2009; 69:16-22.
|
[36] |
Cano LQ, Lavery DN, Bevan CL. Mini-review: foldosome regulation of androgen receptor action in prostate cancer. Mol Cell Endocrinol 2013; 369:52-62.
|
[37] |
Picard D. The role of heat-shock proteins in the regulation of steroid receptor function. In: Freedman LP, editor. Molecular Biology of Steroid and Nuclear Hormone Receptors. Progress in Gene Expression. Boston, MA: Birkh?user; 1998. p. 1-18.
|
[38] |
Fang Y, Fliss AE, Robins DM, Caplan AJ. Hsp90 regulates androgen receptor hormone binding affinity in vivo. J Biol Chem 1996; 271:28697-702.
|
[39] |
Zoubeidi A, Zardan A, Beraldi E, Fazli L, Sowery R, Rennie P, et al. Cooperative interactions between androgen receptor (AR) and heat-shock protein 27 facilitate AR transcriptional activity. Cancer Res 2007; 67:10455-65.
|
[40] |
Grabowska MM, Kelly SM, Reese AL, Cates JM, Case TC, Zhang J, et al. Nfib regulates transcriptional networks that control the development of prostatic hyperplasia. Endocrinology 2016; 157:1094-109.
|
[41] |
Zhao Y, Tindall DJ, Huang H. Modulation of androgen receptor by FOXA1 and FOXO1 factors in prostate cancer. Int J Biol Sci 2014; 10:614-9.
|
[42] |
Dehm SM, Tindall DJ. Molecular regulation of androgen action in prostate cancer. J Cell Biochem 2006; 99:333-44.
|
[43] |
Nash C, Boufaied N, Mills IG, Franco OE, Hayward SW, Thomson AA. Genome-wide analysis of AR binding and comparison with transcript expression in primary human fetal prostate fibroblasts and cancer associated fibroblasts. Mol Cell Endocrinol 2018; 471:1-14.
|
[44] |
Isaacs JT. Prostate stem cells and benign prostatic hyperplasia. Prostate 2008; 68:1025-34.
|
[45] |
Paris DB, Taggart DA, Shaw G, Temple-Smith PD, Renfree MB. Changes in semen quality and morphology of the reproductive tract of the male tammar wallaby parallel seasonal breeding activity in the female. Reproduction 2005; 130:367-78.
|
[46] |
Siwela AA, Tam WH. Ultrastructural changes in the prostate gland of a seasonally breeding mammal, the grey squirrel (Sciurus carolinensis Gmelin). J Anat 1984; 138:153-62.
|
[47] |
Kurita T, Wang YZ, Donjacour AA, Zhao C, Lydon JP, O’Malley BW, et al. Paracrine regulation of apoptosis by steroid hormones in the male and female reproductive system. Cell Death Differ 2001; 8:192-200.
|
[48] |
Wang Y, Sudilovsky D, Zhang B, Haughney PC, Rosen MA, Wu DS, et al. A human prostatic epithelial model of hormonal carcinogenesis. Cancer Res 2001; 61:6064-72.
|
[49] |
Shabsigh A, Chang DT, Heitjan DF, Kiss A, Olsson CA, Puchner PJ, et al. Rapid reduction in blood flow to the rat ventral prostate gland after castration: preliminary evidence that androgens influence prostate size by regulating blood flow to the prostate gland and prostatic endothelial cell survival. Prostate 1998; 36:201-6.
|
[50] |
Mendel CM. The free hormone hypothesis: a physiologically based mathematical model. Endocr Rev 1989; 10:232-74.
|
[51] |
Laurent MR, Hammond GL, Blokland M, Jardí F, Antonio L, Dubois V, et al. Sex hormone-binding globulin regulation of androgen bioactivity in vivo: validation of the free hormone hypothesis. Sci Rep 2016; 6:35539.
pmid: 27748448
|
[52] |
Harman SM, Metter EJ, Tobin JD, Pearson J, Blackman MR. Baltimore longitudinal study of aging. Longitudinal effects of aging on serum total and free testosterone levels in healthy men. Baltimore longitudinal study of aging. J Clin Endocrinol Metab 2001; 86:724-31.
|
[53] |
Gray A, Feldman HA, McKinlay JB, Longcope C. Age, disease, and changing sex hormone levels in middle-aged men: results of the massachusetts male aging study. J Clin Endocrinol Metab 1991; 73:1016-25.
|
[54] |
DePrimo SE, Diehn M, Nelson JB, Reiter RE, Matese J, Fero M, et al. Transcriptional programs activated by exposure of human prostate cancer cells to androgen. Genome Biol 2002; 3:RESEARCH0032. https://doi.org/10.1186/gb-2002-3-7-research0032.
pmid: 12537562
|
[55] |
Wang Q, Carroll JS, Brown M. Spatial and temporal recruitment of androgen receptor and its coactivators involves chromosomal looping and polymerase tracking. Mol Cell 2005; 19:631-42.
|
[56] |
Cunha GR, Chung LW, Shannon JM, Taguchi O, Fujii H. Hormone- induced morphogenesis and growth: role of mesenchymal-epithelial interactions. Recent Prog Horm Res 1983; 39:559-98.
|
[57] |
Wu CT, Altuwaijri S, Ricke WA, Huang SP, Yeh S, Zhang C, et al. Increased prostate cell proliferation and loss of cell differentiation in mice lacking prostate epithelial androgen receptor. Proc Natl Acad Sci U S A 2007; 104:12679-84.
|
[58] |
Nantermet PV, Xu J, Yu Y, Hodor P, Holder D, Adamski S, et al. Identification of genetic pathways activated by the androgen receptor during the induction of proliferation in the ventral prostate gland. J Biol Chem 2004; 279:1310-22.
|
[59] |
Rokhlin OW, Taghiyev AF, Guseva NV, Glover RA, Chumakov PM, Kravchenko JE, et al. Androgen regulates apoptosis induced by TNFR family ligands via multiple signaling pathways in LNCaP. Oncogene 2005; 24:6773-4.
|
[60] |
Gao S, Lee P, Wang H, Gerald W, Adler M, Zhang L, et al. The androgen receptor directly targets the cellular Fas/FasLassociated death domain protein-like inhibitory protein gene to promote the androgen-independent growth of prostate cancer cells. Mol Endocrinol 2005; 19:1792-802.
|
[61] |
Vander Griend DJ, Litvinov IV, Isaacs JT. Conversion of androgen receptor signaling from a growth suppressor in normal prostate epithelial cells to an oncogene in prostate cancer cells involves a gain of function in c-Myc regulation. Int J Biol Sci 2014; 10:627-42.
|
[62] |
Rossi R, Zatelli MC, Valentini A, Cavazzini P, Fallo F, del Senno L, et al. Evidence for androgen receptor gene expression and growth inhibitory effect of dihydrotestosterone on human adrenocortical cells. J Endocrinol 1998; 159:373-80.
|
[63] |
Rossi R, Zatelli MC, Franceschetti P, Maestri I, Magri E, Aguiari G, et al. Inhibitory effect of dihydrotestosterone on human thyroid cell growth. J Endocrinol 1996; 151:185-94.
|
[64] |
Xin L, Teitell MA, Lawson DA, Kwon A, Mellinghoff IK, Witte ON. Progression of prostate cancer by synergy of AKT with genotropic and nongenotropic actions of the androgen receptor. Proc Natl Acad Sci U S A 2006; 103:7789-94.
|
[65] |
Shah RB, Mehra R, Chinnaiyan AM, Shen R, Ghosh D, Zhou M, et al. Androgen-independent prostate cancer is a heterogeneous group of diseases: lessons from a rapid autopsy program. Cancer Res 2004; 64:9209-16.
|
[66] |
van Bokhoven A, Varella-Garcia M, Korch C, Johannes WU, Smith EE, Miller HL, et al. Molecular characterization of human prostate carcinoma cell lines. Prostate 2003; 57:205-25.
|
[67] |
Zegarra-Moro OL, Schmidt LJ, Huang H, Tindall DJ. Disruption of androgen receptor function inhibits proliferation of androgen-refractory prostate cancer cells. Cancer Res 2002; 62:1008-13.
|
[68] |
Yang Q, Fung KM, Day WV, Kropp BP, Lin HK. Androgen receptor signaling is required for androgen-sensitive human prostate cancer cell proliferation and survival. Cancer Cell Int 2005; 5:8. https://doi.org/10.1186/1475-2867-5-8.
doi: 10.1186/1475-2867-5-8
pmid: 15813967
|
[69] |
Dehm SM, Tindall DJ. Androgen receptor structural and functional elements: role and regulation in prostate cancer. Mol Endocrinol 2007; 21:2855-63.
|
[70] |
Snoek R, Cheng H, Margiotti K, Wafa LA, Wong CA, Wong EC, et al. In vivo knockdown of the androgen receptor results in growthinhibitionandregressionofwell-established, castrationresistant prostate tumors. Clin Cancer Res 2009; 15:39-47.
|
[71] |
Zuckerman S. The endocrine control of the prostate: (section of urology). Proc R Soc Med 1936; 29:1557-68.
|
[72] |
White JW. The results of double castration in hypertrophy of the prostate. Ann Surg 1895; 22:1-80.
|
[73] |
Wu CP, Gu FL. The prostate in eunuchs. Prog Clin Biol Res 1991; 370:249-55.
|
[74] |
Pirke KM, Doerr P. Age related changes in free plasma testosterone, dihydrotestosterone and oestradiol. Acta Endocrinol 1975; 80:171-8.
|
[75] |
Trifiro MD, Parsons JK, Palazzi-Churas K, Bergstrom J, Lakin C, Barrett-Connor E. Serum sex hormones and the 20- year risk of lower urinary tract symptoms in communitydwelling older men. BJU Int 2010; 105:1554-9.
|
[76] |
Marks LS, Mazer NA, Mostaghel E, Hess DL, Dorey FJ, Epstein JI, et al. Effect of testosterone replacement therapy on prostate tissue in men with late-onset hypogonadism: a randomized controlled trial. J Am Med Assoc 2006; 296:2351-61.
|
[77] |
Belanger A, Candas B, Dupont A, Cusan L, Diamond P, Gomez JL, et al. Changes in serum concentrations of conjugated and unconjugated steroids in 40- to 80-year-old men. J Clin Endocrinol Metab 1994; 79:1086-90.
|
[78] |
Hammerer PG, McNeal JE, Stamey TA. Correlation between serum prostate specific antigen levels and the volume of the individual glandular zones of the human prostate. J Urol 1995; 153:111-4.
|
[79] |
Weber JP, Oesterling JE, Peters CA, Partin AW, Chan DW, Walsh PC. The influence of reversible androgen deprivation on serum prostate-specific antigen levels in men with benign prostatic hyperplasia. J Urol 1989; 141:987-92.
|
[80] |
McConnell JD, Bruskewitz R, Walsh P, Andriole G, Lieber M Holtgrewe HL, et al. The effect of finasteride on the risk of acute urinary retention and the need for surgical treatment among men with benign prostatic hyperplasia. Finasteride long-term efficacy and safety study group. N Engl J Med 1998; 338:557-63.
|
[81] |
McConnell JD, Roehrborn CG, Bautista OM, Andriole Jr GL, Dixon CM, Kusek JW, et al. The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. N Engl J Med 2003; 349:2387-98.
|
[82] |
Bjornerem A, Straume B, Midtby M, F?nneb? V, Sundsfjord J, Svartberg J, et al. Endogenous sex hormones in relation to age, sex, lifestyle factors, and chronic diseases in a general population: the Tromso study. J Clin Endocrinol Metab 2004; 89:6039-47.
|
[83] |
Ricke WA, shii K, Ricke EA, Simko J, Wang Y, Hayward SW, et al. Steroid hormones stimulate human prostate cancer progression and metastasis. Int J Cancer 2006; 118:2123-31.
|
[84] |
Bernoulli J, Yatkin E, Konkol Y, Talvitie EM, Santti R, Streng T. Prostatic inflammation and obstructive voiding in the adult Noble rat: impact of the testosterone to estradiol ratio in serum. Prostate 2008; 68:1296-306.
|
[85] |
Nicholson TM, Ricke EA, Marker PC, Miano JM, Mayer RD, Timms BG, et al. Testosterone and 17b-estradiol induce glandular prostatic growth, bladder outlet obstruction, and voiding dysfunction in male mice. Endocrinology 2012; 153:5556-65.
|
[86] |
Mahapokai W, Van Sluijs FJ, Schalken JA. Models for studying benign prostatic hyperplasia. Prostate Cancer Prostatic Dis 2000; 3:28-33.
|
[87] |
Hieble JP. Animal models for benign prostatic hyperplasia. Handb Exp Pharmacol 2011: 69-79.
|
[88] |
Nicholson TM, Ricke WA. Androgens and estrogens in benign prostatic hyperplasia: past, present and future. Differentiation 2011; 82:184-99.
|
[89] |
McVary KT. A review of combination therapy in patients with benign prostatic hyperplasia. Clin Ther 2007; 29:387-98.
|
[90] |
Bierhoff E, Vogel J, Benz M, Giefer T, Wernert N, Pfeifer U. Stromal nodules in benign prostatic hyperplasia. Eur Urol 1996; 29:345-54.
|
[91] |
Theyer G, Kramer G, Assmann I, Sherwood E, Preinfalk W, Marberger M, et al. Phenotypic characterization of infiltrating leukocytes in benign prostatic hyperplasia. Lab Investig 1992; 66:96-107.
|
[92] |
Bushman WA, Jerde TJ. The role of prostate inflammation and fibrosis in lower urinary tract symptoms. Am J Physiol Renal Physiol 2016; 311:F817-21. https://doi.org/10.1152/ajprenal.00602.2015.
|
[93] |
Jerde TJ, Bushman W. IL-1 induces IGF-dependent epithelial proliferation in prostate development and reactive hyperplasia. Sci Signal 2009; 2:ra49. https://doi.org/10.1126/scisignal.2000338.
pmid: 19724062
|
[94] |
Dinarello CA. Historical insights into cytokines. Eur J Immunol 2007; 37(Suppl1):S34-45.
|
[95] |
Kramer G, Marberger M. Could inflammation be a key component in the progression of benign prostatic hyperplasia? Curr Opin Urol 2006; 16:25-9.
|
[96] |
Ribal MJ. The link between benign prostatic hyperplasia and inflammation. Eur Urol Suppl 2013; 12:103-9.
doi: 10.1016/S1569-9056(13)61515-8
|
[97] |
Torkko KC, Wilson RS, Smith EE, Kusek JW, van Bokhoven A, Lucia EMSE. Prostate biopsy markers of inflammation are associated with risk of clinical progression of benign prostatic hyperplasia: findings from the MTOPS study. J Urol 2015; 194:454-61.
|
[98] |
Strand DW, Aaron L, Henry G, Franco OE, Hayward SW. Isolation and analysis of discreet human prostate cellular populations. Differentiation 2016; 91:139-51.
|
[99] |
Taoka R, Tsukuda F, Ishikawa M, Haba R, Kakehi Y. Association of prostatic inflammation with down-regulation of macrophage inhibitory cytokine-1 gene in symptomatic benign prostatic hyperplasia. J Urol 2004; 171:2330-5.
|
[100] |
Wang X, Lin WJ, Izumi K, Jiang Q, Lai KP, Xu D, et al. Increased infiltrated macrophages in benign prostatic hyperplasia (BPH): role of stromal androgen receptor in macrophage-induced prostate stromal cell proliferation. J Biol Chem 2012; 287:18376-85.
|
[101] |
Galdiero MR, Bonavita E, Barajon I, Garlanda C, Mantovani A, Jaillon S. Tumor associated macrophages and neutrophils in cancer. Immunobiology 2013; 218:1402-10.
|
[102] |
Lin-Tsai O, Clark PE, Miller NL, Fowke JH, Hameed O, Hayward SW, et al. Surgical intervention for symptomatic benign prostatic hyperplasia is correlated with expression of the AP-1 transcription factor network. Prostate 2014; 74:669-79.
|
[103] |
Austin DC, Strand DW, Love HL, Franco OE, Grabowska MM, Miller NL, et al. NF-kappaB and androgen receptor variant expression correlate with human BPH progression. Prostate 2016; 76:491-511.
|
[104] |
Austin DC, Strand DW, Love HL, Franco OE, Grabowska MM, Miller NL, et al. NF-kappaB and androgen receptor variant 7 induce expression of SRD5A isoforms and confer 5ARI resistance. Prostate 2016; 76:1004-18.
|
[105] |
DeGraff DJ, Grabowska MM, Case TC, Yu X, Herrick MK, Hayward WJ, et al. FOXA1 deletion in luminal epithelium causes prostatic hyperplasia and alteration of differentiated phenotype. Lab Investig 2014; 94:726-39.
|
[106] |
Yu X, Cates JM, Morrissey C, You C, Grabowska MM, Zhang J, et al. SOX2 expression in the developing, adult, as well as, diseased prostate. Prostate Cancer Prostatic Dis 2014; 17:301-9.
|
[107] |
Lai KP, Yamashita S, Vitkus S, Shyr CR, Yeh S, Chang C. Suppressed prostate epithelial development with impaired branching morphogenesis in mice lacking stromal fibromuscular androgen receptor. Mol Endocrinol 2012; 26:52-66.
|
[108] |
Niu Y, Altuwaijri S, Yeh S, Lai KP, Yu S, Chuang KH, et al. Targeting the stromal androgen receptor in primary prostate tumors at earlier stages. Proc Natl Acad Sci U S A 2008; 105:12188-93.
|
[109] |
Singh M, Jha R, Melamed J, Shapiro E, Hayward SW, Lee P. Stromal androgen receptor in prostate development and cancer. Am J Pathol 2014; 184:2598-607.
|
[110] |
Wang Z, Tufts R, Haleem R, Cai X. Genes regulated by androgen in the rat ventral prostate. Proc Natl Acad Sci USA 1997; 94:12999-3004.
|
[111] |
Bauman DR, Steckelbroeck S, Peehl DM, Penning TM. Transcript profiling of the androgen signal in normal prostate, benign prostatic hyperplasia, and prostate cancer. Endocrinology 2006; 147:5806-16.
|
[112] |
Aaron-Brooks LM, Sasaki T, Vickman RE, Wei L, Franco OE, Ji Y, et al. Hyperglycemia and T cell infiltration are associated with stromal and epithelial prostatic hyperplasia in the nonobese diabetic mouse. Prostate 2019; 79:980-93.
|
[113] |
Zhang B, Kwon OJ, Henry G, Malewska A, Wei X, Zhang L, et al. Non-cell-autonomous regulation of prostate epithelial homeostasis by androgen receptor. Mol Cell 2016; 63:976-89.
|
[114] |
Xu D, Wang X, Jiang C, Ruan Y, Xia S, Wang X. The androgen receptor plays different roles in macrophage-induced proliferation in prostate stromal cells between transitional and peripheral zones of benign prostatic hypertrophy. EXCLI J 2017; 16:939-48.
|
[1] |
Gede Wirya Kusuma Duarsa,Yudit Anastasia Sari,Anak Agung Gde Oka,Kadek Budi Santosa,I Wayan Yudiana,Pande Made Wisnu Tirtayasa,Ida Bagus Putra Pramana,Yudhistira Pradnyan Kloping. Serum testosterone and prostate-specific antigen levels are major risk factors for prostatic volume increase among benign prostatic hyperplasia patients[J]. Asian Journal of Urology, 2021, 8(3): 289-297. |
[2] |
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[3] |
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[4] |
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[5] |
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[6] |
Ieva Eringyte,Joanna N. Zamarbide Losada,Sue M. Powell,Charlotte L. Bevan,Claire E. Fletcher. Coordinated AR and microRNA regulation in prostate cancer[J]. Asian Journal of Urology, 2020, 7(3): 233-250. |
[7] |
Yezi Zhu,Jun Luo. Regulation of androgen receptor variants in prostate cancer[J]. Asian Journal of Urology, 2020, 7(3): 251-257. |
[8] |
Chui Yan Mah,Zeyad D. Nassar,Johannes V. Swinnen,Lisa M. Butler. Lipogenic effects of androgen signaling in normal and malignant prostate[J]. Asian Journal of Urology, 2020, 7(3): 258-270. |
[9] |
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[10] |
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[11] |
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[12] |
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[13] |
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[14] |
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[15] |
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