Seyit Erkan EYYÜPOĞLU, Orhun SİNANOĞLU, Sinan EKİCİ, Memduh AYDIN, Mete ÇEK

Rat Penil Erektil Dokusunda Medikal ve Cerrahi Kastrasyonun Neden Olduğu Apoptozun Karşılaştırmalı Değerlendirilmesi

Amaç: Siproteron asetat CPA ve cerrahi orşiektominin rat penil erektil dokusundaki apoptotik etkisini Bax proteinine bağlı olarak değerlendirmek. Yöntem: Postpubertal Wistar Albino ratlar üç gruba ayrıldı. ilk gruba A bilateral orşiektomi n=10 , ikinci gruba B haftada bir 14 gün süreyle 15 mg intramusküler CPA uygulaması n=10 yapıldı. Üçüncü grup C; sham opere kontrol grubu n=10 olarak alındı. Tüm ratlar postoperatif 14. günde sakrifiye edilip penil kavernöz cisimleri blok olarak alındı, Bax proteinine karşı oluşturulmuş anti-mouse IgG içerikli miyarla immünohistokimyasal olarak boyandı ve kavernözal alanlar değişik büyütmelerle mikroskop altında incelendi. Gruplar arasındaki Bax ekspresyonundaki farklı- lıklar one way ANOVA ile değerlendirildi. Bulgular: Proksimal, mid ve distal penil kesitler arasında apoptosis bakımından fark olmadığı görüldü. Cerrahi kastrasyon grubunun penil apoptotik derecesi CPA grubununkinden yüksek bulundu p

Anahtar Kelimeler:

Apoptoz, penil, kavernöz, erektil doku, cerrahi kastrasyon, siproteron asetat

Comparative Evaluation of Medical versus Surgical Castration on Rat Penile Erectile Tissue Apoptosis

Aim: To evaluate the apoptotic effect of Ciproterone acetate CPA and surgical orchidectomy on rat penile erectile tissue on the basis of Bax protein. Methods: Postpubertal Wistar Albino rats were divided in three groups: First group A underwent bilateral orchidectomy n=10 , second group B received 15 mg intramuscular CPA n=10 every two weeks for 14 days. Third group C; sham operated was taken as control n=10 . All rats were sacrified at 14th day, their cavernous bodies were taken en bloc, stained immunohistochemically with a reagent containing anti-mouse IgG against Bax protein and, cavernous sections were evaluated under microscope with different magnifications. Bax expression differences among groups were analysed with one way ANOVA. Results: No apoptotic difference among proximal, mid and distal penile sections was found. The apoptotic index in surgically castrated group was superior compared to CPA treated group p

Keywords:

Apoptosis, penile, cavernous, erectile tissue, surgical castration, ciproterone acetate,

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1. Huggins C, Hodges CV: Studies on prostate cancer: effect of castration, oestrogen and androgen injection on serum phosphatases in metastatic carcinoma of the prostate. Cancer Res 1941: 293-297.
2. Narayan P.: Neoplasms of prostate gland: Smith’s General Urology. Tanagho, E.A., McAninch, J.W. (eds), Practise-Hall international Inc.17th edition 2008; pp: 348-353.
3. Kavoussi LR, Novick AC, Partin AW and Peters CA, eds. Campbell Walsh-Urology, 9th Edition. Philadelphia, WB Saunders Elsevier 2007; sect VI, pp. 718-738.
4. Iversen P, Tyrrell CJ, Kaisary AV, Anderson JB, van Poppel H, Tammela TLJ et al. Bicalutamide monotherapy compared with castration in patients with nonmetastic locally advanced prostate cancer: 6,3 years of follow-up. J Urol 2000 Vol.164, 1579-1582.
5. A; Plymate SR; Katz PG. Visually stimulated erection in castrated men J Urol 1995; 153(3 Pt 1): 650-652.
6. Rousseau L; Dupont A; Labrie F; Couture M. Sexuality changes in prostate cancer patients receiving anti hormonal therapy combining the antiandrogen flutamide with medical (LHRH agonist) or surgical castration. Arch Sex Behav 1988; 17(1): 87-98.
7. Clark JA; Wray NP; Ashton CM. Living with treatment decisions: regrets and quality of life among men treated for metastatic prostate cancer [In Process Citation] J Clin Oncol 2001; 19(1): 72-80.
8. Schroeder FH; Collette L; de Reijke TM; Whelan P. Prostate cancer treated by anti-androgens: is sexual function preserved? EORTC Genitourinary Group. European Organization for Research and Treatment of Cancer. Br J Cancer 2000; 82(2): 283-290.
9. Cooper AJ; Cernovovsky Z. The effects of cyproterone acetate on sleeping and waking penile erections in paedophiles: possible implications for treatment. Can J Psychiatry 1992; 37(1): 33-39.
10. Bradford JM; Pawlak A. Double-blind placebo crossover study of cyproterone acetate in the treatment of the paraphilias. Arch Sex Behav 1993; 22(5): 383-402
11. Zhang XH; Hu LQ; Zheng XM; Li SW. Apoptosis in rat erectile tissue induced by castration. Asian J Androl 1999; 1(4): 181-185.
12. Seftel AD; Maclennan GT; Chen ZJ; Liu S; Ferguson K; Deoreo G; et al: Loss of TGF beta, apoptosis, and bcl2 in erectile dysfunction and upregulation of p53 and HIF-1alpha in diabetes-associated erectile dysfunction. Mol Urol 1999; 3(2): 103-107.
13. Klein LT, Miller MI, Buttyan R, Raffo AJ, Burchard M, Devris G, et al Apoptosis in the rat penis after penile denervation. J Urol Vol 158, 1997; 626-630.
14. Sabsigh R, Raymond JF, Olsson CA, O’toole K, Buttyan R: Androgen induction of DNA synthesis in the rat penis. Urol 52(4), 1988 p: 723-728.
15. Alıcı B, Gümüfltafl MK, Özkara H, Akkufl E, Demirel G, Yencilek F, et al. Apoptosis in the erectile tissues of diabetic and healthy rats. BJU Int 2000; 85, 326-329.
16. Cartledge J. Correspondence to Apoptosis in the erectile tissues of diabetic and healthy rats. BJU Int 2000; 85, 563-564.
17. Herbert M User, John C Hairston, Kevin E McKenna, Carol A Podlasek, David J Zelner, Kevin T McVary. Decreased weight, protein content and apoptosis in denervated rat penis. J Urol 2001; Vol.165, No.5 supp
18. Anti-Mouse, HRP/AEC Ultravision detection system. Labvision Corp., Fremont, U.S.A.
19. Kerr JF; Wyllie AH; Currie AR: Apoptosis: A basic biological phenomenon with wide-ranging implication in tissue kinetics. Br J Cancer 1972; 26: 239-246.
20. Kerr JF: Shrinkage necrosis: a distinct mode of cell death. J Pathol 1971; 105: 13-20.
21. Korsmeyer SJ; Shutter JR; Veis DJ; Merry DE; Oltva ZN: Bcl-2/bax: A rheostat that regulates anti-oxidant pathway and cell death. Sem Cancer Biol 1993; 4:327-332.
22. Bates S. Vousden KH: p53 in signaling checkpoint arrest or apoptosis. Curr Opin Genetics Develop 1996; 6:12-18.
23. Miyashita T; Krajewski S; Krajewska M; Wang HG; Lin HK; Liebermann DA et al: Tumour suppressor p53 is a regular bcl-2 and bax gene expression in vitro and in vivo. Oncogene 1994; 9:1799-1805.
24. Baskin LS; Sutherland RS; Di Sandro MJ; Hayward SW; Lipschutz J; Cunha GR. The effect of testosterone on androgen receptors and human penile growth. J Urol 1997; 158(3 Pt 2): 1113-1118.
25. Shabsigh R. The effects of testosterone on the cavernous tissue and erectile function. World J Urol 1997; 15(1): 21-26.
26. Penson DF; Ng C; Rajfer J; Gonzalez-Cadavid NF. Adrenal control of erectile function and nitric oxide synthase in the rat penis. Endocrinology 1997; 138(9): 3925-3932.
27. Baba K; Yajima M; Carrier S; Akkus E; Reman J; Nunes L et al: Effect of testosterone on the number of NADPH diaphorase-staining nerve fibres in the rat corpus cavernosum and dorsal nerve. Urology 2000; 1;56(3):533-538.
28. Lugg JA, Rajfer J, and Gonzales- Cadavid NF: Dihydrotestosterone is the active androgen in the maintenance of nitric oxide-mediated penil erection in the rat. Endocrinology 1995; 136:1495-1501.
29. Bakircioglu ME; Sievert KD; Nunes L; Lau A; Lin CS; Lue TF: Decreased trabecular smooth muscle and caveolin-1 expression in the penile tissue of aged rats. J Urol 2001; 166(2): 734-738.