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研究雄性小鼠神经系统缺乏雄激素受体对阴部球海绵体神经肌系统的影响。

Characterization of the spinal nucleus of the bulbocavernosus neuromuscular system in male mice lacking androgen receptor in the nervous system.

机构信息

Centre National de la Recherche Scientifique Unité Mixte de Recherche 7224, and Université Pierre et Marie Curie, 75005 Paris Cedex 05, France.

出版信息

Endocrinology. 2012 Jul;153(7):3376-85. doi: 10.1210/en.2012-1001. Epub 2012 May 14.

Abstract

Motoneurons in the spinal nucleus of the bulbocavernosus (SNB) and their target bulbocavernosus (BC) and levator ani (LA) muscles play a role in male copulation and fertility. Testosterone (T) induces sexual differentiation of this SNB neuromuscular system during development and maintains its activation in adulthood. In the rat, T-induced effects mostly involve the androgen receptor (AR). However, the role of central AR in T-induced effects remains to be studied with pertinent genetic models. We addressed this question by using specific motoneuron immunolabeling and retrograde tracing in mice selectively disrupted for AR in the nervous system. This work reveals that nervous system AR is not required either for T-induced development of BC-LA muscles and perinatal sparing of SNB motoneurons from atrophy or for adult sensitivity of BC-LA muscles to T. By contrast, loss of AR expression in the nervous system resulted in SNB motoneurons having smaller somata and shorter dendrites than controls. We studied the effects of adult castration and T supplementation on SNB cell morphology in control and mutant males; these experiments showed that central AR is involved in the developmental regulation of soma size and dendritic length and in the adult maintenance of soma size of SNB motoneurons. T seemed to act indirectly through BC-LA muscles to maintain dendritic length in adulthood. Our results also suggest that central AR functions may contribute to normal activity of SNB motoneurons and perineal muscles because mutant mice displayed diminished copulatory behavior and fertility.

摘要

阴部神经核中的运动神经元及其靶器官阴部球海绵体肌和肛提肌在雄性交配和生育中起作用。睾丸酮(T)在发育过程中诱导该阴部神经肌肉系统的性分化,并在成年期维持其激活。在大鼠中,T 诱导的效应主要涉及雄激素受体(AR)。然而,中枢 AR 在 T 诱导效应中的作用仍需用相关的遗传模型进行研究。我们通过使用特定的运动神经元免疫标记和逆行示踪技术,在神经系统中选择性敲除 AR 的小鼠中解决了这个问题。这项工作表明,中枢神经系统中的 AR 既不需要 T 诱导的 BC-LA 肌肉发育和 SNB 运动神经元免受围产期萎缩的影响,也不需要成年 BC-LA 肌肉对 T 的敏感性。相比之下,神经系统中 AR 的表达缺失导致 SNB 运动神经元的胞体较小,树突较短。我们研究了成年去势和 T 补充对对照和突变雄性 SNB 细胞形态的影响;这些实验表明,中枢 AR 参与了胞体大小和树突长度的发育调节,以及成年 SNB 运动神经元胞体大小的维持。T 似乎通过 BC-LA 肌肉间接作用于成年时维持树突长度。我们的结果还表明,中枢 AR 的功能可能有助于 SNB 运动神经元和会阴部肌肉的正常活动,因为突变小鼠表现出交配行为和生育能力下降。

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