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Effects of estrogen on age-related changes in muscarinic responsiveness of the urinary bladder and lumbosacral dorsal root ganglion cells in female rats

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Abstract

The aim of this study was to investigate estrogen’s effect on age-related changes in bladder function. Female Wistar rats were divided into three groups that included young rats (3-month-old) (YR), old rats (13-month-old) (OR), and old rats given subcutaneous treatments of estradiol for 6 weeks (OR + E). The groups were evaluated for (i) micturition behavior, (ii) changes of detrusor contractility and frequency of detrusor contraction in response to muscarinic stimulation in cystometrograms, (iii) messenger RNA (mRNA) expression of the muscarinic receptor subtype in the detrusor muscle, as measured by real-time polymerase chain reaction, and (iv) the immunoreactivity of P2X3, CGRP, and substance P in the lumbosacral dorsal root ganglia. There were no significant changes for the average micturition volumes or micturition frequencies seen among the three groups. Moreover, there were no significant differences in the proportion of the immunoreactivities of P2X3, CGRP, and substance P in afferent neurons among these three groups. However, an intravenous administration of muscarine significantly increased the frequency during continuous cystometrograms in the OR and OR + E groups. In these groups, there was a significant increase in the expression of the M2 receptor mRNAs as compared to YR. It appears that the up-regulation of the M2 receptor may lead to a decreased intercontraction interval by muscarinic stimuli. OR + E rats showed a significant increase in bladder weight as compared to the OR group. The muscarine-stimulated contractility of the detrusor in the cystometrogram also exhibited a significant increase in the OR + E group as compared to the OR group, which resulted from estrogen-induced functional hypertrophy of the detrusor muscle. These findings suggest that as little as 6 weeks of estrogen treatment is capable of improving the detrusor contractility, although the treatment contributes little to the storage phase of the micturition cycle.

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Acknowledgments

We are grateful to Professor Eiji Nanba for his invaluable suggestions and comments. We also would like to thank Ms. Yumako Miura, Ms. Kaori Adachi, Ms. Mayumi Yamanaka, and Mr. Norihisa Itaki for their excellent technical assistance.

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Authors and Affiliations

  1. Division of Urology, Department of Surgery, Tottori University Faculty of Medicine, 86 Nishi, Yonago, Tottori, 683-8504, Japan

    Takeshi Watanabe, Mayuko Matsumoto, Sumiyo Toji & Ikuo Miyagawa

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  1. Takeshi Watanabe
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  2. Mayuko Matsumoto
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  3. Sumiyo Toji
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  4. Ikuo Miyagawa
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Correspondence to Takeshi Watanabe.

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Watanabe, T., Matsumoto, M., Toji, S. et al. Effects of estrogen on age-related changes in muscarinic responsiveness of the urinary bladder and lumbosacral dorsal root ganglion cells in female rats. Mol Cell Biochem 318, 53–61 (2008). https://doi.org/10.1007/s11010-008-9856-8

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  • DOI: https://doi.org/10.1007/s11010-008-9856-8

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