Autocrine androgen action is essential for Leydig cell maturation and function, and protects against late-onset Leydig cell apoptosis in both mice and men.
Autocrine androgen action is essential for Leydig cell maturation and function, and protects against late-onset Leydig cell apoptosis in both mice and men.
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DOI：
10.1096/fj.14-255729
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发表时间：
2015-03
期刊：
影响因子：
--
通讯作者：
Smith LB
中科院分区：
文献类型：
--
作者：
O'Hara L;McInnes K;Simitsidellis I;Morgan S;Atanassova N;Slowikowska-Hilczer J;Kula K;Szarras-Czapnik M;Milne L;Mitchell RT;Smith LB
睾丸间质细胞的数量和功能随着男性年龄的增长而下降，低睾酮与所有“西方”心脏代谢紊乱有关。然而，是否扰动雄激素的行动在成年Leydig细胞谱系倾向于个人这种迟发性变性仍然未知。为了解决这一问题，我们建立了一种新的小鼠模型，其中从胎儿期开始，雄激素受体（AR）从大约75%的成年Leydig干细胞/细胞祖细胞中去除（Leydig细胞AR敲除小鼠），允许通过与相邻的保留AR的Leydig细胞、来自同窝对照的睾丸和人睾丸比较来询问自分泌Leydig细胞AR信号传导的特定作用，包括完全雄激素不敏感综合征（CAIS）患者。这表明，自分泌AR信号转导对于达到最终的Leydig细胞数量是不必要的，但对于成年期Leydig细胞成熟和类固醇生成酶的调节是必不可少的。此外，这些研究表明，间质细胞中的自分泌AR信号传导可能通过对抗异常雌激素信号传导来保护小鼠生精上皮的迟发型变性，并抑制成年小鼠和CAIS患者的间质细胞凋亡。我们的结论是，睾丸间质细胞内的自分泌雄激素作用对于精子发生的终身支持以及睾丸间质细胞的发育和终身健康至关重要。奥哈拉湖，McInnes，K.，西米特赛德利斯岛，摩根，S.，Atanassova，N.，Slowikowska-Hilczer，J.，Kula，K.，Szarras-Czapnik，M.，米尔恩湖米切尔河，巴西-地T.，史密斯湖，澳-地B。自分泌雄激素的作用对睾丸间质细胞的成熟和功能是必不可少的，并保护小鼠和男性的迟发性睾丸间质细胞凋亡。
Leydig cell number and function decline as men age, and low testosterone is associated with all “Western” cardio-metabolic disorders. However, whether perturbed androgen action within the adult Leydig cell lineage predisposes individuals to this late-onset degeneration remains unknown. To address this, we generated a novel mouse model in which androgen receptor (AR) is ablated from ∼75% of adult Leydig stem cell/cell progenitors, from fetal life onward (Leydig cell AR knockout mice), permitting interrogation of the specific roles of autocrine Leydig cell AR signaling through comparison to adjacent AR-retaining Leydig cells, testes from littermate controls, and to human testes, including from patients with complete androgen insensitivity syndrome (CAIS). This revealed that autocrine AR signaling is dispensable for the attainment of final Leydig cell number but is essential for Leydig cell maturation and regulation of steroidogenic enzymes in adulthood. Furthermore, these studies reveal that autocrine AR signaling in Leydig cells protects against late-onset degeneration of the seminiferous epithelium in mice and inhibits Leydig cell apoptosis in both adult mice and patients with CAIS, possibly via opposing aberrant estrogen signaling. We conclude that autocrine androgen action within Leydig cells is essential for the lifelong support of spermatogenesis and the development and lifelong health of Leydig cells.—O’Hara, L., McInnes, K., Simitsidellis, I., Morgan, S., Atanassova, N., Slowikowska-Hilczer, J., Kula, K., Szarras-Czapnik, M., Milne, L., Mitchell, R. T., Smith, L. B. Autocrine androgen action is essential for Leydig cell maturation and function, and protects against late-onset Leydig cell apoptosis in both mice and men.
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影响因子：
4.1
作者：
Chen H;Ge RS;Zirkin BR
通讯作者：
Zirkin BR
影响因子：
4.8
作者：
De Gendt, K;Atanassova, N;Verhoeven, G
通讯作者：
Verhoeven, G
DOI：
10.1073/pnas.2536828100
发表时间：
2003-12-23
影响因子：
11.1
作者：
He, WM;Barak, Y;Evans, RM
通讯作者：
Evans, RM
影响因子：
29
作者：
Eguchi J;Wang X;Yu S;Kershaw EE;Chiu PC;Dushay J;Estall JL;Klein U;Maratos-Flier E;Rosen ED
通讯作者：
Rosen ED
影响因子：
3.6
作者：
Brinster, CJ;Ryu, BY;Orwig, KE
通讯作者：
Orwig, KE