Abstract
Purpose:
Testosterone affects male development, maturation and aging but limited data exist on testosterone effects on the juvenile genitourinary system. We hypothesized that testosterone has bladder and kidney developmental effects, and investigated this in juvenile male rats.
Materials and Methods:
To examine the testosterone effect 21-day-old prepubertal male Wistar rats were divided into 3 groups of 12 each, including sham orchiectomy as controls, and bilateral orchiectomy with vehicle and bilateral orchiectomy with testosterone. Starting at age 28 days (week 0) testosterone enanthate (5 mg/100 gm) or vehicle was injected weekly. Testosterone was measured at study week 0 before injection, and at weeks 1, 6 and 16. Whole bladders and kidneys were evaluated for androgen receptor, bladder collagen-to-smooth muscle ratio, and renal morphometry and immunohistochemistry.
Results:
Testosterone was not detectable at week 0 in all groups. It remained undetectable at weeks 1, 6 and 16 in the orchiectomy plus vehicle group. Testosterone levels were physiological in controls and rats with orchiectomy plus testosterone but levels were higher in the latter than in the former group. Rats with orchiectomy plus testosterone had increased bladder-to-body and kidney-to-body weight ratios (p <0.01 and <0.05, respectively), and decreased collagen-to-smooth muscle ratio than the orchiectomy plus vehicle and control groups. Rats with orchiectomy plus testosterone had a lower renal total glomerular count (p <0.01) but increased androgen receptor density.
Conclusions:
In juvenile male rats testosterone was associated with increased bladder and renal mass, and increased bladder smooth muscle. Testosterone associated kidneys also appeared to have fewer but larger glomeruli. These data support an important role for sex hormones in structural and functional development of the bladder and kidney.
References
- 1 : The effect of ovariectomy and long-term estrogen replacement on bladder structure and function in the rat. J Urol2002; 168: 1265. Link, Google Scholar
- 2 : Structural changes in the bladder walls of pregnant and hormone-treated rats: correlation with bladder dynamics. BJU Int2004; 94: 1366. Google Scholar
- 3 : Location and concentration of estrogen, progesterone, and androgen receptors in the bladder and urethra of the rabbit. Neurourol Urodyn2005; 14: 87. Google Scholar
- 4 : Effects of different sex hormones on male rabbit urodynamics: an experimental study. Horm Res2003; 60: 215. Google Scholar
- 5 : Androgen replacement therapy in the aging male. Rev Urol2003; 5: 216. Google Scholar
- 6 : Comparative study of antigen retrieval heating methods: microwave, microwave and pressure cooker, autoclave, and steamer. Biotech Histochem1996; 71: 263. Google Scholar
- 7 : Effects of androgenic-anabolic steroids in athletes. Sports Med2004; 34: 513. Google Scholar
- 8 : Effect of exercise training and anabolic androgenic steroids on hemodynamics, glycogen content, angiogenesis and apoptosis of cardiac muscle in adult male rats. Int J Health Sci (Qassim)2013; 7: 47. Google Scholar
- 9 : Variations in serum FSH, LH and testosterone levels in male rats from birth to sexual maturity. J Reprod Fertil1975; 42: 121. Google Scholar
- 10 : The laboratory rat: relating its age with human's. Int J Prev Med2013; 4: 624. Google Scholar
- 11 : Effects of ovariectomy or orchidectomy and estradiol valerate or testosterone enanthate replacement on serum insulin in rats. Pak J Biol Sci2008; 11: 306. Google Scholar
- 12 : Type III collagen decreases in normal fetal bovine bladder development. J Urol1994; 152: 688. Link, Google Scholar
- 13 : Bladder wall abnormalities in myelodysplastic bladders: a computer assisted morphometric analysis. J Urol1991; 145: 1024. Link, Google Scholar
- 14 : The effect of testosterone replacement therapy on bladder functions and histology in orchiectomized mature male rats. Urology2010; 75: 886. Google Scholar
- 15 : Effects of castration and hormone replacement in the urinary bladder of rats: structural, ultrastructural, and biochemical analysis. J Androl2012; 33: 684. Google Scholar
- 16 : Testosterone supplementation's effects on age-related bladder remodeling—experimental study in rats. Aging Male2013; 16: 102. Google Scholar
- 17 : The effect of testosterone alone and testosterone + estradiol therapy on bladder functions and smooth muscle/collagen content in surgically menopause induced rats. Maturitas2008; 60: 248. Google Scholar
- 18 : The impact of gender on the progression of chronic renal disease. Am J Kidney Dis1995; 25: 515. Google Scholar
- 19 : The effect of anabolic steroids on the gastrointestinal system, kidneys, and adrenal glands. Curr Sports Med Rep2006; 5: 104. Google Scholar
- 20 : Development of focal segmental glomerulosclerosis after anabolic steroid abuse. J Am Soc Nephrol2010; 21: 163. Google Scholar
- 21 : Effects of supraphysiologic doses of testosterone on mood and aggression in normal men: a randomized controlled trial. Arch Gen Psychiatry2000; 57: 133. Google Scholar
- 22 : Stereologic methods and their application in kidney research. J Am Soc Nephrol1999; 10: 1100. Google Scholar
- 23 : Recovery from release of ureteral obstruction in the rat: relationship to nephrogenesis. Kidney Int2002; 61: 2033. Google Scholar
- 24 : Sonographic renal parenchymal and pelvicaliceal areas: new quantitative parameters for renal sonographic followup. J Urol1996; 156: 725. Link, Google Scholar
- 25 : Intrauterine growth retardation leads to a permanent nephron deficit in the rat. Pediatr Nephrol1994; 8: 175. Google Scholar
- 26 : Altered nephrogenesis due to maternal diabetes is associated with increased expression of IGF-II/mannose-6-phosphate receptor in the fetal kidney. Diabetes2001; 50: 1069. Google Scholar
- 27 : Relationship between weight at birth and the number and size of renal glomeruli in humans: a histomorphometric study. Kidney Int2000; 58: 770. Google Scholar
- 28 : Early defect in branching morphogenesis of the ureteric bud in induced nephron deficit. Kidney Int1996; 50: 783. Google Scholar
- 29 : Effects of early postnatal hypernutrition on nephron number and long-term renal function and structure in rats. Am J Physiol Renal Physiol2007; 293: F1944. Google Scholar
- 30 : Effects of sex on renal structure. Nephron2002; 90: 139. Google Scholar