Human prostatic urethra expresses vitamin D receptor and responds to vitamin D receptor ligation.
BACKGROUND
Chronic inflammation is now considered a determinant of benign prostatic hyperplasia (BPH), promoting, together with the hormonal milieu, prostate overgrowth and lower urinary tract symptoms (LUTS). Prostatic urethra actively participates in determining progression of LUTS associated with BPH.


OBJECTIVE
To investigate the expression of the vitamin D receptor (VDR) and the ability of the VDR agonist elocalcitol to reduce inflammatory responses in human prostatic urethra (hPU) cells.


METHODS
Human prostatic urethra, prostate and bladder neck were obtained from patients affected by BPH. Immunohistochemical studies for VDR expression were performed in tissue samples, from which primary cell cultures were also derived. In hPU cells, proliferation and chemiotaxis were studied, along with Rho kinase (ROCK) activity (MYPT-1 phosphorylation) by western blot. Quantitative RT-PCR was performed for VDR, cyclooxygenase (COX-2), and interleukin (IL)-8 expression.


RESULTS
Urethra displays higher VDR expression compared to prostate and bladder neck tissues. The VDR agonist elocalcitol partially reverts COX-2 and IL-8 mRNA upregulation induced by a pro-inflammatory cytokine mixture (IL-17, interferon-γ, tumor necrosis factor-α) and inhibits cell migration in urethral cells. Elocalcitol prevents activation of ROCK, as previously demonstrated in bladder and prostate cell cultures.


CONCLUSIONS
Our results suggest that prostatic urethra is, within the lower urinary tract, a novel target for VDR agonists, as shown by the capacity of elocalcitol to inhibit ROCK activity and to limit inflammatory responses in human primary urethra cells.
Comeglio
P
P
Andrology Unit, Department of Clinical Physiopathology, University of Florence, V.le Pieraccini 6, 50139 Florence, Italy.
Chavalmane
A K
AK
Fibbi
B
B
Filippi
S
S
Marchetta
M
M
Marini
M
M
Morelli
A
A
Penna
G
G
Vignozzi
L
L
Vannelli
G B
GB
Adorini
L
L
Maggi
M
M
D000368:Aged; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000494:pharmacology; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D015870:Gene Expression; D006801:Humans; D008024:Ligands; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011467:Prostate / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D011470:Prostatic Hyperplasia / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D018167:Receptors, Calcitriol / Q000819:agonists* / Q000235:genetics* / Q000378:metabolism; D014521:Urethra / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D001743:Urinary Bladder / Q000378:metabolism / Q000473:pathology
C487049:BXL628; D016207:Cytokines; D008024:Ligands; D018167:Receptors, Calcitriol; D002117:Calcitriol
Biochem Biophys Res Commun. 2008 Apr 25;369(1):149-56
18155661
J Immunol. 2007 Jan 1;178(1):145-53
17182549
World J Urol. 2005 Dec;23(6):362-7
16283327
J Sex Med. 2009 Jan;6(1):91-106
19170840
J Pharmacol Exp Ther. 2004 Jun;309(3):1148-53
14769832
Prostate. 2009 Apr 1;69(5):480-93
19107880
Lab Invest. 2003 Aug;83(8):1131-46
12920242
J Biol Chem. 2003 Apr 11;278(15):13578-84
12574166
J Pharmacol Exp Ther. 2004 Jan;308(1):54-8
14532355
J Biol Chem. 1999 Mar 26;274(13):8506-15
10085083
Urol Clin North Am. 2008 Feb;35(1):109-15; vii
18061029
Prostate. 2002 Jun 1;52(1):43-58
11992619
Am J Physiol Endocrinol Metab. 2006 Aug;291(2):E315-22
16507601
Recent Results Cancer Res. 2003;164:29-42
12899512
J Steroid Biochem Mol Biol. 2007 Mar;103(3-5):689-93
17241782
Mol Pharmacol. 2002 Feb;61(2):277-84
11809851
Eur J Biochem. 1997 Nov 15;250(1):63-71
9431991
J Clin Endocrinol Metab. 2000 Jul;85(7):2576-83
10902811
J Immunol. 2004 Aug 15;173(4):2280-7
15294940
Physiol Rev. 2003 Oct;83(4):1325-58
14506307
Eur J Endocrinol. 2004 Apr;150(4):591-603
15080791
J Cardiovasc Pharmacol. 2008 Oct;52(4):369-74
18841072
J Urol. 2001 Jul;166(1):172-6
11435849
Mol Hum Reprod. 2007 Mar;13(3):181-7
17227815
Obstet Gynecol. 1989 Jul;74(1):69-74
2733945
Br J Urol. 1997 Jul;80(1):84-90
9240186
Prostate. 2007 Feb 15;67(3):234-47
17163492
J Clin Endocrinol Metab. 2005 Feb;90(2):962-72
15572423
J Surg Res. 2007 Oct;142(2):239-45
17574271
BJU Int. 2003 Feb;91(3):196-200
12581003
Annu Rev Biochem. 2000;69:145-82
10966456
J Biol Chem. 1998 Feb 6;273(6):3551-61
9452482
World J Urol. 2002 Apr;19(6):390-396
28386659
Eur Urol. 2007 Oct;52(4):964-72
17618043
Arthritis Rheum. 2008 Nov;58(11):3366-76
18975348
J Biol Chem. 2003 Dec 5;278(49):49378-85
14507914
Pharmacol Rev. 1993 Sep;45(3):253-308
8248281
Nat Clin Pract Rheumatol. 2008 Aug;4(8):404-12
18594491
Br J Pharmacol. 2003 Mar;138(5):757-66
12642376
Can J Urol. 1994 Jan;1(1):1-4
12834558
Br J Pharmacol. 2003 Dec;140(7):1292-302
14581180
Radiol Clin North Am. 2006 Sep;44(5):749-56, ix
17030225
Neurourol Urodyn. 2004;23(7):618-22
15382181
Anticancer Res. 2006 Jul-Aug;26(4A):2525-30
16886660
Pediatr Radiol. 2007 Sep;37(9):851-62; quiz 945
17572890
Trends Pharmacol Sci. 2001 Jan;22(1):32-9
11165670
Atherosclerosis. 2008 Aug;199(2):237-47
18436225
Gastroenterology. 2003 May;124(5):1180-7
12730857
Nat Clin Pract Urol. 2008 Apr;5(4):211-9
18301417
Pharmacol Rev. 2004 Dec;56(4):581-631
15602011
Eur Urol. 2002 Jul;42(1):1-6
12121721
J Endocrinol Invest. 2006 Jul-Aug;29(7):665-74
16957418
J Urol. 2004 Aug;172(2):748-52
15247775
Carcinogenesis. 2006 Sep;27(9):1883-93
16624828
J Steroid Biochem Mol Biol. 2007 Mar;103(3-5):552-7
17368184
Neurourol Urodyn. 2007 Oct;26(6 Suppl):948-54
17696159
Eur Urol. 2007 May;51(5):1202-16
17182170