The effect of ovariectomy and long-term estrogen replacement on bladder structure and function in the rat.
ABSTRACT PURPOSE The use of estrogen replacement therapy for treating postmenopausal urinary incontinence is a controversial topic. We examined the behavioral, cystometric and histological changes that occur with long-term estrogen depletion and supplementation in rat bladders to determine the role of menopause in lower urinary tract dysfunction. MATERIALS AND METHODS A total of 40 female Sprague-Dawley rats were placed into 1 of 3 groups, including bilateral ovariectomy, bilateral ovariectomy plus estrogen replacement and control. The estrogen replaced group received a 0.25 mg. 16-week sustained release pellet (Innovative Research of America, Sanasota, Florida) placed subcutaneously. After surgery voiding frequency and volume were measured in 24-hour periods by placing animals in metabolic cages. After 16 weeks the rats underwent catheterization and continuous cystometry. The bladder was then removed and stained with Gomori trichrome. The collagen-to-smooth muscle density ratio was calculated for each specimen using current imaging software. RESULTS There was no significant difference in voiding patterns in the 3 groups, as measured by volume and voiding frequency. Cystometric data showed a trend toward higher voiding pressure, threshold pressure, baseline pressure and mean inter-voiding pressure in the ovariectomy group compared with the estrogen and control groups, although there was no statistical significance. Histological studies showed a higher mean collagen-to-smooth muscle ratio plus or minus standard deviation in the ovariectomy group (0.807 +/- 0.204) than in the ovariectomy plus estrogen replacement (0.709 +/- 0.118) and control (0.700 +/- 0.129) groups (p <0.05). Furthermore, when histological and cystometric data were compared for individual samples, we found a direct correlation of mean inter-voiding pressure (a measure of bladder instability) with the collagen-to-smooth muscle ratio (p <0.05). CONCLUSIONS Long-term estrogen replacement is beneficial for treating postmenopausal urinary incontinence.
- SourceAvailable from: Linda M. Dairiki Shortliffe[Show abstract] [Hide abstract]
ABSTRACT: Purpose: Testosterone (T) affects male development, maturation, and aging, but limited data exist on testosterone effects on the juvenile genitourinary system. We hypothesized that T has bladder and kidney developmental effects, and investigated this in juvenile male rats. Materials and Methods: To examine T effect, prepubertal male Wistar rats (age 21 days) were divided among 3 groups: sham orchiectomy--control (S, N=12), bilateral orchiectomy and vehicle (OV, N=12), and bilateral orchiectomy and T (OT, N=12). From age 28 days (week 0, W=0) testosterone enanthate (T, 5 mg/100g) or vehicle were injected weekly. T was measured at W=0 (before injection), and weeks 1, 6, and 16 (W=0, 1,6,16). Whole bladders and kidneys were evaluated for androgen receptor (AR), bladder collagen to smooth muscle ratio (C/M), and renal morphometry and immunohistochemistry. Results: T was not detectable (ND) at W=0 for all groups, and remained ND at W=1, 6,16 for OV rats. T levels were physiologic in S and OT rats, but OT had higher levels than S rats. OT rats had increased bladder/body weight (BW, P<0.01), kidney/BW (p<0.05) ratios, and decreased C/M ratio compared with OV and S rats. OT rats had lower renal total glomerular count (p<0.01) but increased AR density. Conclusions: In juvenile male rats T was associated with increased bladder and renal mass and increased bladder smooth muscle. T associated kidneys also appeared to have fewer but larger glomeruli. These data support an important role for sex hormones in structural and functional development within the bladder and kidney.The Journal of urology 06/2014; · 3.75 Impact Factor
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ABSTRACT: To reveal the exogenous effects of sex hormones on cell proliferation and apoptosis in the detrusor muscle of ovariectomized rat urinary bladder. Proliferating cell nuclear antigen (PCNA) and in-situ apoptosis detection kit were used to evaluate cell proliferation and death in the detrusor muscle of castrated female rats after 1 day, 3 days, and 7 days of supplementary sex steroid hormone administration, including estrogen, progesterone, and testosterone. The percentage of cells positive for PCNA (proliferative index) and for apoptosis (apoptotic index) in various groups was calculated. When compared to the group of bilateral ovariectomy without hormonal supplementation, the groups given 3 days and 7 days of estrogen supplementation (p = 0.031 and p = 0.005, respectively) and the group given 7 days of combined supplementation with estrogen and progesterone (p = 0.044) had a significant increase in the proliferative indices. A significant decrease of apoptotic index was found in the group given 7 days of estrogen supplementation when compared to bilateral ovariectomy without hormonal supplementation (p = 0.035). Exogenous estrogen supplementation stimulates proliferation and slows down apoptosis in the detrusor muscle of ovariectomized rat urinary bladder, an effect not counteracted by concomitant use of progesterone. Our results may have clinical implications for estrogen supplementation in offering benefits to menopausal women with lower urinary tract syndromes, based on evaluating the relationship between cell apoptosis and cell proliferation.Taiwanese journal of obstetrics & gynecology 09/2013; 52(3):335-40.
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ABSTRACT: The typical antipsychotic haloperidol is a highly effective treatment for schizophrenia but its use is limited by a number of serious, and often irreversible, motor side effects. These adverse drug reactions, termed extrapyramidal syndromes (EPS), result from an unknown pathophysiological mechanism. One theory relates to the observation that the haloperidol metabolite HPP+ (4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]-pyridinium) is structurally similar to MPP+ (1-methyl-4-phenylpyridinium), a neurotoxin responsible for an irreversible neurodegenerative condition similar to Parkinson's disease. To determine whether HPP+ contributes to haloperidol-induced EPS, we measured brain HPP+ and haloperidol levels in strains of mice at high (C57BL/6J and NZO/HILtJ) and low (BALB/cByJ and PWK/PhJ) liability to haloperidol-induced EPS following chronic treatment (7-10 adult male mice per strain). Brain levels of HPP+ and the ratio of HPP+ to haloperidol were not significantly different between the haloperidol-sensitive and haloperidol-resistant strain groups (P=0.50). Within each group, however, strain differences were seen (P<0.01), indicating that genetic variation regulating steady-state HPP+ levels exists. Since the HPP+ levels that we observed in mouse brain overlap the range of those detected in post-mortem human brains following chronic haloperidol treatment, the findings from this study are physiologically relevant to humans. The results suggest that strain differences in steady-state HPP+ levels do not explain sensitivity to haloperidol-induced EPS in the mice we studied.NeuroToxicology 10/2013; · 2.65 Impact Factor