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Diminished androgen levels are linked to irritable bowel syndrome and cause bowel dysfunction in mice
The Journal of Clinical Investigation ( IF 15.9 ) Pub Date : 2021 , DOI: 10.1172/jci150789 Daniella Rastelli 1, 2 , Ariel Robinson 1 , Valentina N Lagomarsino 1 , Lynley T Matthews 2 , Rafla Hassan 3 , Kristina Perez 1 , William Dan 4 , Peter D Yim 4 , Madison Mixer 1 , Aleksandra Prochera 1 , Amy Shepherd 1 , Liang Sun 5 , Kathryn Hall 6 , Sarah Ballou 3 , Anthony Lembo 3 , Judy Nee 3 , Meenakshi Rao 1, 2
The Journal of Clinical Investigation ( IF 15.9 ) Pub Date : 2021 , DOI: 10.1172/jci150789 Daniella Rastelli 1, 2 , Ariel Robinson 1 , Valentina N Lagomarsino 1 , Lynley T Matthews 2 , Rafla Hassan 3 , Kristina Perez 1 , William Dan 4 , Peter D Yim 4 , Madison Mixer 1 , Aleksandra Prochera 1 , Amy Shepherd 1 , Liang Sun 5 , Kathryn Hall 6 , Sarah Ballou 3 , Anthony Lembo 3 , Judy Nee 3 , Meenakshi Rao 1, 2
Affiliation
Functional gastrointestinal disorders (FGIDs) have prominent sex differences in incidence, symptoms, and treatment response that are not well understood. Androgens are steroid hormones present at much higher levels in males than females and could be involved in these differences. In adults with irritable bowel syndrome (IBS), a FGID that affects 5% to 10% of the population worldwide, we found that free testosterone levels were lower than those in healthy controls and inversely correlated with symptom severity. To determine how this diminished androgen signaling could contribute to bowel dysfunction, we depleted gonadal androgens in adult mice and found that this caused a profound deficit in gastrointestinal transit. Restoring a single androgen hormone was sufficient to rescue this deficit, suggesting that circulating androgens are essential for normal bowel motility in vivo. To determine the site of action, we probed androgen receptor expression in the intestine and discovered, unexpectedly, that a large subset of enteric neurons became androgen-responsive upon puberty. Androgen signaling to these neurons was required for normal colonic motility in adult mice. Taken together, these observations establish a role for gonadal androgens in the neural regulation of bowel function and link altered androgen levels with a common digestive disorder.
中文翻译:
雄激素水平降低与肠易激综合征有关,并导致小鼠肠道功能障碍
功能性胃肠道疾病 (FGID) 在发病率、症状和治疗反应方面存在显着的性别差异,目前尚不清楚。雄激素是类固醇激素,男性体内的含量比女性高得多,并且可能与这些差异有关。在患有肠易激综合征 (IBS) 的成人中,这是一种影响全球 5% 至 10% 人口的 FGID,我们发现游离睾酮水平低于健康对照组,并且与症状严重程度呈负相关。为了确定这种减少的雄激素信号如何导致肠道功能障碍,我们耗尽了成年小鼠的性腺雄激素,发现这会导致胃肠道运输严重不足。恢复单一的雄激素就足以弥补这一缺陷,表明循环雄激素对于体内正常的肠道运动是必不可少的。为了确定作用部位,我们探测了肠道中雄激素受体的表达,并意外地发现,大部分肠道神经元在青春期时变得对雄激素有反应。雄激素信号传导到这些神经元是成年小鼠正常结肠运动所必需的。总之,这些观察结果确定了性腺雄激素在肠道功能的神经调节中的作用,并将雄激素水平的改变与常见的消化系统疾病联系起来。雄激素信号传导到这些神经元是成年小鼠正常结肠运动所必需的。总之,这些观察结果确定了性腺雄激素在肠道功能的神经调节中的作用,并将雄激素水平的改变与常见的消化系统疾病联系起来。雄激素信号传导到这些神经元是成年小鼠正常结肠运动所必需的。总之,这些观察结果确定了性腺雄激素在肠道功能的神经调节中的作用,并将雄激素水平的改变与常见的消化系统疾病联系起来。
更新日期:2022-01-19
中文翻译:
雄激素水平降低与肠易激综合征有关,并导致小鼠肠道功能障碍
功能性胃肠道疾病 (FGID) 在发病率、症状和治疗反应方面存在显着的性别差异,目前尚不清楚。雄激素是类固醇激素,男性体内的含量比女性高得多,并且可能与这些差异有关。在患有肠易激综合征 (IBS) 的成人中,这是一种影响全球 5% 至 10% 人口的 FGID,我们发现游离睾酮水平低于健康对照组,并且与症状严重程度呈负相关。为了确定这种减少的雄激素信号如何导致肠道功能障碍,我们耗尽了成年小鼠的性腺雄激素,发现这会导致胃肠道运输严重不足。恢复单一的雄激素就足以弥补这一缺陷,表明循环雄激素对于体内正常的肠道运动是必不可少的。为了确定作用部位,我们探测了肠道中雄激素受体的表达,并意外地发现,大部分肠道神经元在青春期时变得对雄激素有反应。雄激素信号传导到这些神经元是成年小鼠正常结肠运动所必需的。总之,这些观察结果确定了性腺雄激素在肠道功能的神经调节中的作用,并将雄激素水平的改变与常见的消化系统疾病联系起来。雄激素信号传导到这些神经元是成年小鼠正常结肠运动所必需的。总之,这些观察结果确定了性腺雄激素在肠道功能的神经调节中的作用,并将雄激素水平的改变与常见的消化系统疾病联系起来。雄激素信号传导到这些神经元是成年小鼠正常结肠运动所必需的。总之,这些观察结果确定了性腺雄激素在肠道功能的神经调节中的作用,并将雄激素水平的改变与常见的消化系统疾病联系起来。