Shift from androgen to estrogen action causes abdominal muscle fibrosis, atrophy, and inguinal hernia in a transgenic male mouse model.
Shift from androgen to estrogen action causes abdominal muscle fibrosis, atrophy, and inguinal hernia in a transgenic male mouse model.
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DOI：
10.1073/pnas.1807765115
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发表时间：
2018-10-30
影响因子：
11.1
通讯作者：
Bulun SE
中科院分区：
文献类型：
--
作者：
Zhao H;Zhou L;Li L;Coon V J;Chatterton RT;Brooks DC;Jiang E;Liu L;Xu X;Dong Z;DeMayo FJ;Stulberg JJ;Tourtellotte WG;Bulun SE
腹股沟疝是影响老年男性最常见的疾病之一。腹股沟疝的一个主要病理基础是纤维化和其他退行性变化，影响腹股沟管附近的下腹部肌肉力量。在这里，我们描述了一个关键的作用，雌激素及其核受体，增强成纤维细胞增殖和肌肉萎缩，导致腹股沟疝。进一步的研究可能揭示雌激素消融在预防老年男性肌肉纤维化或疝气中的潜在作用。腹股沟疝主要发生在老年男性中，超过四分之一的男性在其一生中会接受腹股沟疝修补术。然而，疝形成背后的潜在机制仍然未知。众所周知，睾酮和雌二醇可以调节骨骼肌质量。我们在此证明，睾酮转化为雌二醇的芳香化酶在下腹部肌肉（LAM）组织引起强烈的纤维化，导致肌肉萎缩和腹股沟疝;芳香化酶抑制剂完全防止这种表型。LAM组织对雌二醇特别敏感，因为它表达非常高水平的雌激素受体-α。雌二醇通过LAM成纤维细胞中的雌激素受体-α激活增殖和纤维化途径，取代萎缩的肌细胞，导致疝形成。这伴随着血清睾酮下降和LAM组织中雄激素受体靶基因表达下降。这些发现为LAM组织纤维化和萎缩提供了一种机制，并提示未来非手术和预防方法在有疝气发生倾向的老年男性亚组中的潜在作用。
Inguinal hernia is one of the most common disorders that affect elderly men. A major pathology underlying inguinal hernia is the fibrosis and other degenerative changes that affect the lower abdominal muscle strength adjacent to the inguinal canal. Here we describe a critical role of estrogen and its nuclear receptor that enhance fibroblast proliferation and muscle atrophy, leading to inguinal hernia. Further research may reveal a potential role of estrogen ablation to prevent muscle fibrosis or hernia in a subset of elderly men. Inguinal hernia develops primarily in elderly men, and more than one in four men will undergo inguinal hernia repair during their lifetime. However, the underlying mechanisms behind hernia formation remain unknown. It is known that testosterone and estradiol can regulate skeletal muscle mass. We herein demonstrate that the conversion of testosterone to estradiol by the aromatase enzyme in lower abdominal muscle (LAM) tissue causes intense fibrosis, leading to muscle atrophy and inguinal hernia; an aromatase inhibitor entirely prevents this phenotype. LAM tissue is uniquely sensitive to estradiol because it expresses very high levels of estrogen receptor-α. Estradiol acts via estrogen receptor-α in LAM fibroblasts to activate pathways for proliferation and fibrosis that replaces atrophied myocytes, resulting in hernia formation. This is accompanied by decreased serum testosterone and decreased expression of the androgen receptor target genes in LAM tissue. These findings provide a mechanism for LAM tissue fibrosis and atrophy and suggest potential roles of future nonsurgical and preventive approaches in a subset of elderly men with a predisposition for hernia development.
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影响因子：
9
作者：
Bay-Nielsen, M;Perkins, FM;Kehlet, H
通讯作者：
Kehlet, H
影响因子：
5.4
作者：
Ahrens-Fath, I;Politz, O;Haendler, B
通讯作者：
Haendler, B
影响因子：
4.8
作者：
BJORN, JC;GARDNER, WU
通讯作者：
GARDNER, WU
影响因子：
--
作者：
Boney-Montoya, Jamie;Ziegler, Yvonne S.;Nardulli, Ann M.
通讯作者：
Nardulli, Ann M.
影响因子：
5.8
作者：
GRAY, A;FELDMAN, HA;LONGCOPE, C
通讯作者：
LONGCOPE, C