Bravo Giselle, Massa Helen, Rose'Meyer Roselyn, Chess-Williams Russ, McDermott Catherine, Sellers Donna J
Centre for Urology Research, Faculty of Health Sciences and Medicine, Bond University, Queensland, Australia.
School of Medical Science, Griffith University, Queensland, Australia.
Naunyn Schmiedebergs Arch Pharmacol. 2017 May;390(5):547-556. doi: 10.1007/s00210-017-1355-6. Epub 2017 Feb 11.
In men, testosterone levels decline by 1% per year after the age of 40. Reduced androgen levels may directly contribute to lower urinary tract symptoms and bladder dysfunction, although the mechanisms are unclear. This study examined the effect of low testosterone and testosterone replacement on key mechanisms involved in local bladder function. Intraluminal release of the mediators ATP and ACh in response to bladder distension was measured in whole bladders from rats 8 weeks following castration, whilst bladder contractility was assessed using isolated strips. Human urothelial cells were cultured under low, physiological and supra-physiological testosterone conditions for 24 h or 5 days, and stretch-induced release of ATP and ACh was measured. Phasic contractile activity of bladder strips, agonist-induced reponses to carbachol and isoprenaline and nerve-evoked contractions were unaffected by castration. The acetylcholinesterase inhibitor neostigmine significantly increased amplitude of phasic activity only in bladder strips following castration, and this was prevented by testosterone replacement. Intraluminal ACh release following bladder distension was significantly reduced following castration, whilst ATP release was unaffected. In contrast, stretch-induced ATP release from urothelial cells was significantly enhanced in low testosterone conditions, whilst ACh release was unaltered. Testosterone-replacement to physiological levels prevented these changes. Whilst androgen deficiency of 8 weeks does not directly affect contractility of bladder smooth muscle, urothelial mediator release is sensitive to changes in testosterone. These changes in mediator release may be an early effect of the decline in testosterone and could affect sensory pathways in the longer term, contributing to the urinary symptoms and bladder dysfunction seen in androgen-deficient men.
男性40岁后，睾酮水平每年下降1%。雄激素水平降低可能直接导致下尿路症状和膀胱功能障碍，尽管其机制尚不清楚。本研究探讨了低睾酮水平及睾酮替代对局部膀胱功能关键机制的影响。在去势8周后的大鼠全膀胱中，测量膀胱扩张时介质ATP和乙酰胆碱（ACh）的腔内释放，同时使用离体膀胱条评估膀胱收缩力。将人尿路上皮细胞在低睾酮、生理睾酮和超生理睾酮条件下培养24小时或5天，然后测量拉伸诱导的ATP和ACh释放。膀胱条的相性收缩活动、激动剂诱导的对卡巴胆碱和异丙肾上腺素的反应以及神经诱发的收缩不受去势影响。乙酰胆碱酯酶抑制剂新斯的明仅在去势后的膀胱条中显著增加相性活动的幅度，而睾酮替代可防止这种情况。去势后膀胱扩张时腔内ACh释放显著减少，而ATP释放不受影响。相反，在低睾酮条件下，拉伸诱导的尿路上皮细胞ATP释放显著增强，而ACh释放未改变。将睾酮替代至生理水平可防止这些变化。虽然8周的雄激素缺乏不会直接影响膀胱平滑肌收缩力，但尿路上皮介质释放对睾酮变化敏感。介质释放的这些变化可能是睾酮下降的早期效应，从长远来看可能影响感觉通路，导致雄激素缺乏男性出现排尿症状和膀胱功能障碍。
