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首页> 外文期刊>Endocrinology >Sexual differentiation of the spinal nucleus of the bulbocavernosus is not mediated solely by androgen receptors in muscle fibers.
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Sexual differentiation of the spinal nucleus of the bulbocavernosus is not mediated solely by androgen receptors in muscle fibers.

机译：球海绵体脊髓核的性别分化不仅仅由肌肉纤维中的雄激素受体介导。

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The spinal nucleus of the bulbocavernosus (SNB) neuromuscular system is a highly conserved and well-studied model of sexual differentiation of the vertebrate nervous system. Sexual differentiation of the SNB is currently thought to be mediated by the direct action of perinatal testosterone on androgen receptors (ARs) in the bulbocavernosus/levator ani muscles, with concomitant motoneuron rescue. This model has been proposed based on surgical and pharmacological manipulations of developing rats as well as from evidence that male rats with the testicular feminization mutation (Tfm), which is a loss of function AR mutation, have a feminine SNB phenotype. We examined whether genetically replacing AR in muscle fibers is sufficient to rescue the SNB phenotype of Tfm rats. Transgenic rats in which wild-type (WT) human AR is driven by a human skeletal actin promoter (HSA-AR) were crossed with Tfm rats. Resulting male HSA-AR/Tfm rats express WT AR exclusively in muscle and nonfunctional Tfm AR in other tissues. We then examined motoneuron and muscle morphology of the SNB neuromuscular system of WT and Tfm rats with and without the HSA-AR transgene. We observed feminine levator ani muscle size and SNB motoneuron number and size in Tfm males with or without the HSA-AR transgene. These results indicate that AR expression in skeletal muscle fibers is not sufficient to rescue the male phenotype of the SNB neuromuscular system and further suggest that AR in other cell types plays a critical role in sexual differentiation of this system.
机译：球囊海绵体（SNB）神经肌肉系统的脊髓核是脊椎动物神经系统的性别分化的高度保守和经过充分研究的模型。目前认为，SNB的性别分化是由围生期睾丸激素对球海绵体/提肛动物肌肉中雄激素受体（ARs）的直接作用介导的，同时伴随着运动神经元的抢救。该模型是根据发育中大鼠的手术和药理操作以及具有睾丸女性化突变（Tfm）（即功能性AR突变丧失）的雄性大鼠具有女性SNB表型的证据提出的。我们检查了遗传替代肌肉纤维中的AR是否足以挽救Tfm大鼠的SNB表型。将其中由人骨骼肌动蛋白启动子（HSA-AR）驱动的野生型（WT）人AR的转基因大鼠与Tfm大鼠杂交。所得雄性HSA-AR / Tfm大鼠仅在肌肉中表达WT AR，而在其他组织中仅表达功能性Tfm AR。然后，我们检查了有和没有HSA-AR转基因的WT和Tfm大鼠的SNB神经肌肉系统的运动神经元和肌肉形态。我们观察了有或没有HSA-AR转基因的Tfm男性的女性提肛肌尺寸和SNB运动神经元数量和尺寸。这些结果表明骨骼肌纤维中的AR表达不足以挽救SNB神经肌肉系统的男性表型，并且进一步表明其他细胞类型中的AR在该系统的性别分化中起关键作用。

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