Watson N V, Freeman L M, Breedlove S M
Department of Psychology, Simon Fraser University, Burnaby, British Columbia, V5A 1S6 Canada.
J Neurosci. 2001 Feb 1;21(3):1062-6. doi: 10.1523/JNEUROSCI.21-03-01062.2001.
The motoneurons of the spinal nucleus of the bulbocavernosus (SNB) and its target muscles, the bulbocavernosus and levator ani, form a sexually dimorphic circuit that is developmentally dependent on androgen exposure and exhibits numerous structural and functional changes in response to androgen exposure in adulthood. Castration of male adult rats causes shrinkage of SNB somata, and testosterone replacement reverses this effect, but the site at which androgen is acting to cause this change is undetermined. We exploited the X-chromosome residency of the androgen receptor (AR) gene to generate androgenized female rats that were heterozygous for the testicular feminization mutant (tfm) AR mutation and that, as a consequence of ontogenetic random X-inactivation, expressed a blend of androgen-sensitive wild-type cells and tfm-affected androgen-insensitive cells in the SNB. Chronic testosterone treatment of adult mosaics increased soma sizes only in androgen-competent wild-type SNB cells. The size of tfm-affected SNB somata in the same animals did not differ from the size of either the wild-type or tfm-affected SNB neurons in control mosaics that did not receive androgen treatment in adulthood. Because the muscle targets of the SNB are known to be uniformly androgen-sensitive in tfm mosaics, this mosaic analysis provides unambiguous evidence that androgenic effects on motoneuron soma size are mediated locally in the SNB. It is possible that the neuronal AR plays a permissive role in coordinating the actions of androgen.
球海绵体肌脊髓核(SNB)的运动神经元及其靶肌肉,即球海绵体肌和提肛肌,形成了一个性别二态性回路,该回路在发育上依赖雄激素暴露,并且在成年期对雄激素暴露会表现出许多结构和功能变化。成年雄性大鼠去势会导致SNB胞体萎缩,而睾酮替代可逆转这种效应,但雄激素发挥作用导致这种变化的部位尚不确定。我们利用雄激素受体(AR)基因位于X染色体上这一特性,培育出了睾丸雌性化突变(tfm)AR突变杂合的雄激素化雌性大鼠,由于个体发育过程中随机的X染色体失活,这些大鼠的SNB中表达了雄激素敏感的野生型细胞和受tfm影响的雄激素不敏感细胞的混合体。对成年嵌合体大鼠进行慢性睾酮处理,仅使雄激素敏感的野生型SNB细胞的胞体增大。在同一动物中,受tfm影响的SNB胞体大小与成年期未接受雄激素处理的对照嵌合体中野生型或受tfm影响的SNB神经元的大小没有差异。由于已知在tfm嵌合体中SNB的肌肉靶标对雄激素均一敏感,这种嵌合体分析提供了明确的证据,表明雄激素对运动神经元胞体大小的影响是在SNB局部介导的。神经元AR可能在协调雄激素的作用中发挥允许作用。