Estrogen replacement avoids the decrease of bladder innervations in ovariectomized adult virgin rats: in vivo stereological study (original) (raw)
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Effect of Estrogen on Bladder Nociception in Rats
The Journal of Urology, 2010
Purpose-We assessed the effect of ovariectomy and estrogen replacement on nociceptive responses to bladder distention in a rat model. Materials and Methods-Female Sprague-Dawley rats (Harlan™) underwent ovariectomy or sham surgery. Visceromotor responses (abdominal contractions) to bladder distention were determined 3 to 4 weeks later under isoflurane anesthesia. In rat subsets estrogen was chronically replaced with a subcutaneous estrogen pellet vs a placebo pellet or acutely replaced by subcutaneous injection 24 hours before testing. Effects of estrogen withdrawal were examined in another group of rats by implanting a pellet and explanting the pellet 24 hours before testing. Uterine weight was measured to assess the estrogen dose. Results-Visceromotor responses to bladder distention were significantly less vigorous in ovariectomized rats vs controls. Acute estrogen replacement increased visceromotor responses in these rats but chronic estrogen replacement did not. Sudden chronic estrogen withdrawal resulted in increased visceromotor responses. Uterine weight was consistent with the physiological estrogen dose. Conclusions-Estrogen alone was not sufficient to produce increased nociceptive responses but an acute decrease in estrogen resulted in increased visceromotor responses. These data suggest that the pronociceptive effects of estrogen may be due to a mismatch between peripheral vs central and/or genomic vs nongenomic effects of the hormone, which occur during rapidly decreasing estrogen levels.
International Urogynecology Journal, 2005
The objective of this study was to investigate the effects of ovariectomy (OVX) and vaginal distension (VD) on leak point pressure (LPP) and pudendal nerve regenerative response in the female rat. Twenty rats underwent OVX 3 days prior to either VD or sham distension. Seventeen rats did not receive OVX but underwent either VD or sham distension. Four days after distension, LPP testing was performed. In situ hybridization for b II tubulin mRNA, an indicator of the neuroregenerative response, was performed on motoneurons of the pudendal nerve. In the non-OVX group, LPP was significantly decreased after VD. After OVX, the difference in LPP between VD and sham rats did not quite reach the level of statistical significance. There was a statistically significant interaction between the effects of OVX and VD on LPP. There was no significant difference in in situ hybridization results between any of the groups. No neuroregenerative response of motoneurons of the pudendal nerve was observed after either VD or OVX.
The Journal of Urology, 2006
We tested the hypothesis that estrogen promotes improvement in urethral function and nerve regeneration following bilateral pudendal nerve crush in ovariectomized female rats. Materials and Methods: A total of 52 female rats underwent ovariectomy 6 days before bilateral pudendal nerve crush. Estrogen and sham capsules were subcutaneously implanted at the time of nerve crush in 16 and 14 of these rats, respectively, while 22 served as unoperated controls. Seven days following nerve crush urethral LPP testing was performed using urethane anesthesia. Spinal cord sections containing motoneurons of Onufrowicz's nucleus were subjected to in situ hybridization to detect the expression of  II tubulin mRNA, a marker of the neuroregenerative response. Results: Mean LPP Ϯ SEM was significantly decreased after pudendal nerve crush in sham treated animals compared to unoperated controls (32.1 Ϯ 6.8 vs 54.4 Ϯ 11.6 cm H 2 O). Rats with an estrogen implant had an LPP of 42.5 Ϯ 16.8 cm H 2 O, which was significantly greater than rats given sham implants and significantly less than unoperated controls. Rats that received an estrogen implant had increased  II tubulin mRNA expression compared to those that received a sham implant.
The Journal of Urology, 1993
Objective: The present study investigated the effects of long-term hormone treatment, including the most commonly prescribed progestin, medroxyprogesterone acetate, during aging on synaptophysin-labeled boutons, a marker of synapses, in the medial prefrontal cortex (mPFC) of rats. Methods: Female Long Evans hooded rats were ovariectomized at middle age (12-13 mo) and were placed in one of four groups: no replacement (n = 5), 17A-estradiol alone (n = 6), estradiol and progesterone (n = 7), or estradiol and medroxyprogesterone acetate (n = 4). Estradiol was administered in the drinking water and progestogens were administered via subcutaneous pellets that were replaced every 90 days. After 7 months of hormone replacement, the animals were euthanized, and the brains were stained for synaptophysin, a membrane component of synaptic vesicles. The density of synaptophysin-labeled boutons was quantified in the mPFC using unbiased stereology and multiplied by the volume of the mPFC to obtain the total number. Results: Animals receiving estradiol and medroxyprogesterone acetate had significantly more synaptophysinlabeled boutons in the mPFC than did animals not receiving replacement (P G 0.03) and those receiving estradiol and progesterone (P G 0.02). In addition, there was a nonsignificant trend for animals receiving estradiol alone to have more synapses than those receiving estradiol and progesterone. Conclusions: This study is the first to examine the effects of estradiol and medroxyprogesterone acetate during rat aging on cortical synaptic number. Estradiol with medroxyprogesterone acetate, but not progesterone, resulted in a greater number of synapses in the mPFC during aging than did no replacement.
Influence of estradiol on micturition thresholds in the rat: involvement of the hypogastric nerve
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2005
Studies have shown that the severity of bladder hyperreflexia induced by acute bladder inflammation varies with the ovarian cycle. These results suggest that the hyperreflexia is modulated by ovarian hormones. Other studies have suggested that such modulation involves the bladder's sympathetic innervation. These hypotheses were tested by assessing the development of bladder hyperreflexia in urethane-anesthetized rats subjected to different hormonal manipulations with or without bilateral hypogastric neurectomy (HYPX). The groups included sham ovariectomy (sham OVX), ovariectomy (OVX), OVX with estradiol replacement (OVX+E), OVX+HYPX, and OVX+HYPX+E. Assessments were performed using repeated cystometrograms (CMGs) to measure micturition thresholds (MT) before and hourly for 3 h after intravesicular treatment with 50% turpentine oil (or olive oil in an OVX+E control group). In the uninflamed bladder, treatment with estradiol increased MTs in the OVX+E group compared with the OVX g...
Neurourology and Urodynamics, 2012
Objective: To evaluate the expression of nerve growth factor (NGF) in the urethra of adult female rats in different hormonal status using immunohistochemical assay. Methods: Forty-eight rats (Rattus norvegicus albinus, Rodentia, Mammalia) from the CEDEME-UNIFESP laboratory animal facility were used in the study. Rats were divided into four groups: group A, 12 non-neutered rats; group B, 12 oophorectomized rats; group C, 12 castrated rats treated with 17b-estradiol for 30 days; and group D, 12 aging rats. Animals were killed by lethal injection and their urethra was removed. NGF expression was evaluated by means of immunohistochemistry using mouse monoclonal primary IgG antibody anti-NGF diluted 1:600, and read under 400Â magnification. Digital analysis of the images was done by Imagelab software. The intensity of the dark brown color was used as a measure of NGF cytoplasmatic expression, and was used to quantify the percentage of epithelial and muscular layer cells showing this neurotrophin. Results: After oophorectomy, rats showed a significant increase in NGF expression in the periurethral muscular layer. Compared with oophorectomized rats, NGF expression increased in the epithelial layer and diminished in the periurethral smooth muscle following estrogen administration. In 18-month-old rats, NGF expression was diminished in both epithelial and muscular layers. Conclusions: Hormonal status led to significant differences in NGF protein expression in urethral epithelium and periurethral smooth muscle. Neurourol. Urodynam. 31:702-705, 2012. ß
Brain research, 2003
Responses of neurons in the gracile nucleus (NG) of female rats to tactile and visceral stimulation change across the estrous cycle [J. Neurosci. 20 (2000) 7722]. To investigate estrogen's role in these changes, responses of NG neurons to tactile and visceral stimuli were examined in three groups: ovariectomized (OVX), OVX with estrogen replacement (OVX+E2), or sham OVX (tested in diestrus; shamOVX-D). The stimuli were: gentle brushing of hindquarter skin, pressure on the cervix, and distention of the uterus, vagina, or colon. After OVX, the magnitude of multi-unit responses to brushing the perineum, hip and tail, but not the foot and leg, were significantly reduced relative to shamOVX-D. OVX+E2 restored this magnitude to the same level as shamOVX-D, but not, as expected, to levels as large as previously observed in proestrus. After OVX, responses of single neurons to stimulation of the uterus, cervix, and colon were more likely to be excitatory (versus inhibitory) than they had...
Life sciences, 1997
Contractile responses induced by carbachol on the detrusor muscle and by noradrenaline on the isolated urethra were compared between ovariectomized rats pretreated with estradiol (50 microg/animal s.c. twice daily for five days), untreated ovariectomized rats and intact animals. In the detrusor muscle, contractions induced by 30 microM carbachol, when normalized with respect to KCl 100 mM-induced contraction, were similar for the three groups. Furthermore, contractions induced by 100 microM noradrenaline in the isolated urethra were not significatively different between groups. However, the pD2 value for noradrenaline was greater in urethral tissue from ovariectomized rats compared with ovariectomized -estrogen treated and control rats. A similar result was found for pD2 values for carbachol-induced contractions on the detrusor muscle. These results suggest that ovariectomy increases the sensitivity of the urinary bladder and urethra to the contractile effects of carbachol and norad...
Effect of Ovariectomy on External Urethral Sphincter Activity in Anesthetized Female Rats
The Journal of Urology, 2011
The postmenopausal hypoestrogen condition is associated with various lower urinary tract dysfunctions, including frequency, urgency, stress urinary incontinence and recurrent urinary infection. We determined whether hypoestrogen induced lower urinary tract dysfunction after ovariectomy is also associated with an alteration in external urethral sphincter activity. Materials and Methods: Bilateral ovariectomy was performed in female Sprague-Dawley® rats and sham operated rats served as controls. Transvesical cystometry and external urethral sphincter electromyogram activity were monitored 4, 6 and 12 weeks after sham operation or bilateral ovariectomy and at 6 weeks in bilaterally ovariectomized rats treated with estrogen. Results: The micturition reflex was elicited in sham operated and bilaterally ovariectomized, urethane anesthetized animals. Post-void residual urine increased and voiding efficiency decreased in rats with 4 to 12 weeks of bilateral ovariectomy. The silent period of external urethral sphincter electromyogram activity was shortened significantly and progressively at increased times after bilateral ovariectomy. These effects were prevented by estradiol treatment. Conclusions: As evidenced by shortening of the external urethral sphincter electromyogram silent period in ovariectomized rats, the disruption of coordination between the external urethral sphincter and the detrusor muscle could decrease urine outflow and in turn voiding efficiency. Estrogen replacement reverses these changes, suggesting that the central pathways responsible for detrusor-sphincter coordination are modulated by gonadal hormones.