The Effect of Testosterone Replacement Therapy on Bladder Functions, Histology, Apoptosis, and Rho-kinase Expression in Bladder Outlet Obstruction and Hypogonadism Rat Model

Overview

Journal Turk J Med Sci

Specialty General Medicine

Date 2021 Jan 2

PMID 33387987

Authors

Baris Saylam

Ozan Efesoy

Rabia Bozdogan Arpaci

Rukiye Nalan Tiftik

Mesut Tek

Kansu Buyukafsar

Murat Bozlu

Selahittin Cayan

Affiliations

Soon will be listed here.

Abstract

Background/aim: The effect of testosterone replacement therapy was investigated on bladder functions, histology, apoptosis as well as Rho-kinase expression in the rat bladder outlet obstruction (BOO) and hypogonadism models.

Materials And Methods: 30 mature male rats divided into 4 groups: sham group (n = 8), BOO group (n = 8), BOO + orchiectomy group (n = 7), BOO + orchiectomy + testosterone (T) treatment group (n = 7). Cystometric findings, apoptosis index, Rho-kinase (ROCK-2) expression, and smooth muscle/collagen ratio were compared.

Results: BOO did not change ROCK-2 expression level, compared to sham group (P > 0.05). However, when compared to BOO group (P < 0.01), BOO + orchiectomy led ROCK-2 increase. The testosterone treatment failed to reverse the up-regulation of ROCK-2 induced by orchiectomy although it tended to lower ROCK-2 level. Compared to sham group (P = 0.002), changes in maximal bladder capacity and leak point pressure were higher (P = 0.026, P = 0.001), and bladder compliance was lower in BOO group. Also, the apoptosis index was different between the two groups (P = 0.380). Smooth muscle/collagen ratio was higher in BOO + orchiectomy + T group than in BOO + orchiectomy group (P = 0.010).

Conclusions: The research draws attention to alternating treatment approaches in case of the presence of hypogonadism and BOO.

References

Lin W, Rehfuss A, Whitbeck C, Juan Y, Chichester P, Mannikarottu A . Effect of letrozole on urinary bladder function in the female rabbit. BJU Int. 2007; 100(6):1391-5. DOI: 10.1111/j.1464-410X.2007.07149.x. View

Cayan S, Canpolat B, Cayan F, Yilmaz N, Kartal A, Oguz I . The effect of chronic inflammatory condition of the bladder and estrogen replacement therapy on bladder functions and histology in surgically menopause and chronic cystitis induced rats. Neurourol Urodyn. 2005; 25(2):194-201. DOI: 10.1002/nau.20158. View

Bing W, Chang S, Hypolite J, DiSanto M, Zderic S, Rolf L . Obstruction-induced changes in urinary bladder smooth muscle contractility: a role for Rho kinase. Am J Physiol Renal Physiol. 2003; 285(5):F990-7. DOI: 10.1152/ajprenal.00378.2002. View

Rajasekaran M, Wilkes N, Kuntz S, Albo M . Rho-kinase inhibition suppresses bladder hyperactivity in spontaneously hypertensive rats. Neurourol Urodyn. 2005; 24(3):295-300. DOI: 10.1002/nau.20122. View

Maggi C, Manzini S, Giuliani S, Meli A . Infravesical outflow obstruction in rats: a comparison of two models. Gen Pharmacol. 1989; 20(3):345-9. DOI: 10.1016/0306-3623(89)90271-1. View

Meikle A, Arver S, Dobs A, Adolfsson J, Sanders S, Middleton R . Prostate size in hypogonadal men treated with a nonscrotal permeation-enhanced testosterone transdermal system. Urology. 1997; 49(2):191-6. DOI: 10.1016/s0090-4295(96)00445-1. View

Wibberley A, Chen Z, Hu E, Hieble J, Westfall T . Expression and functional role of Rho-kinase in rat urinary bladder smooth muscle. Br J Pharmacol. 2003; 138(5):757-66. PMC: 1573720. DOI: 10.1038/sj.bjp.0705109. View

Greenland J, Brading A . The effect of bladder outflow obstruction on detrusor blood flow changes during the voiding cycle in conscious pigs. J Urol. 2000; 165(1):245-8. DOI: 10.1097/00005392-200101000-00072. View

Tek M, Balli E, Cimen B, Efesoy O, Oguz I, Cayan S . The effect of testosterone replacement therapy on bladder functions and histology in orchiectomized mature male rats. Urology. 2009; 75(4):886-90. DOI: 10.1016/j.urology.2009.08.016. View

10.

Turna B, Cinar M, Canda A, Orhan E, Tiftik N, Nazli O . Role of Rho-kinase in contractions of ureters from rabbits with unilateral ureteric obstruction. BJU Int. 2007; 100(5):1166-71. DOI: 10.1111/j.1464-410X.2007.07152.x. View

11.

Buyukafsar K, Levent A, Ark M . Expression of Rho-kinase and its functional role in the contractile activity of the mouse vas deferens. Br J Pharmacol. 2003; 140(4):743-9. PMC: 1574068. DOI: 10.1038/sj.bjp.0705479. View

12.

Kim J, Han J, Kwon T, Choo M . Effects of Oral Rho Kinase Inhibitor Fasudil on Detrusor Overactivity after Bladder Outlet Obstruction in Rats. Low Urin Tract Symptoms. 2015; 5(2):96-100. DOI: 10.1111/j.1757-5672.2012.00169.x. View

13.

Andersson K, Arner A . Urinary bladder contraction and relaxation: physiology and pathophysiology. Physiol Rev. 2004; 84(3):935-86. DOI: 10.1152/physrev.00038.2003. View

14.

Somlyo A, Somlyo A . Signal transduction by G-proteins, rho-kinase and protein phosphatase to smooth muscle and non-muscle myosin II. J Physiol. 2000; 522 Pt 2:177-85. PMC: 2269761. DOI: 10.1111/j.1469-7793.2000.t01-2-00177.x. View

15.

Celayir S . Effects of different sex hormones on male rabbit urodynamics: an experimental study. Horm Res. 2003; 60(5):215-20. DOI: 10.1159/000074034. View

16.

Pandita R, Persson K, Hedlund P, Andersson K . Testosterone-induced prostatic growth in the rat causes bladder overactivity unrelated to detrusor hypertrophy. Prostate. 1998; 35(2):102-8. DOI: 10.1002/(sici)1097-0045(19980501)35:2<102::aid-pros3>3.0.co;2-l. View

17.

Erben R, Eberle J, Stahr K, Goldberg M . Androgen deficiency induces high turnover osteopenia in aged male rats: a sequential histomorphometric study. J Bone Miner Res. 2000; 15(6):1085-98. DOI: 10.1359/jbmr.2000.15.6.1085. View

18.

Buyukafsar K, Akca T, Tiftik R, Sahan-Firat S, Aydin S . Contribution of Rho-kinase in human gallbladder contractions. Eur J Pharmacol. 2006; 540(1-3):162-7. DOI: 10.1016/j.ejphar.2006.04.028. View

19.

Ogut O, Brozovich F . Regulation of force in vascular smooth muscle. J Mol Cell Cardiol. 2003; 35(4):347-55. DOI: 10.1016/s0022-2828(03)00045-2. View