ESTROGENIC EFFECTS IN ANDROGEN SENSITIVE MOTONEURONS

雌激素对雄激素敏感运动神经元的影响

• 批准号: 2883160
• 负责人: DALE R SENGELAUB
• 金额: $ 16.45万
• 依托单位: TRUSTEES OF INDIANA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-03-01 至 2002-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2883160
• 关键词: androgens; aromatase; dendrites; electrophysiology; estrogens; gap junctions; histochemistry /cytochemistry; hormone regulation /control mechanism; immunocytochemistry; laboratory rat; male; motor neurons; neurogenesis; protein localization; sex differentiation; spinal cord

DESCRIPTION: Estrogen is considered to be the primary metabolite responsible for the differentiation of sexually dimorphic brain regions. In contrast, the development of sexually dimorphic nuclei in the spinal cord has been considered to be regulated strictly by androgens. Testing the validity and limitations of this apparent dichotomy in the critical forms of steroid hormones involved in sexual differentiation of the nervous system and potential differences in their site of action is the focus of this proposal. Using a simple hormone-sensitive neuromuscular system in the rat spinal cord, three different features of this system will be examined: aspects of motoneuron morphology (histochemistry), distribution of critical enzymes (immunocytochemistry), and neuromuscular function (electrophysiology). Synergistic effects of estrogen and androgen, the necessity of estrogen availability, the role of supraspinal and local interneuronal, estrogen-sensitive afferents, and the effects of naturally occurring estrogen levels in morphological development will be assessed. Because the transient expression of aromatase has been reported in a variety of developing neural structures, postnatal spinal cords will be assayed for the presence of aromatase. The role of estrogen in regulating the development of gap junctions, which are common in these motoneurons, will also be examined. Changes in motoneuron excitability during development are likely responsible for the onset of spinally mediated reflexes, and the role of estrogen and androgen in the development of several functional properties of these hormone-sensitive motoneurons will be assessed. Because recent evidence suggests that estrogen is in fact involved in spinal cord masculinization, these studies may help in unifying our understanding of the process of sexual differentiation across the developing mammalian central nervous system.

描述：雌激素被认为是主要代谢产物 负责性别二态性大脑区域的分化。 在 相比之下，脊髓中性二态核的发育 被认为受到雄激素的严格调节。 测试 这种明显的二分法在批判形式中的有效性和局限性 类固醇激素参与神经系统的性别分化 其作用位点的潜在差异是本文的重点 提议。 在大鼠中使用简单的激素敏感神经肌肉系统 脊髓，将检查该系统的三个不同特征： 运动神经元形态（组织化学）方面，关键分布 酶（免疫细胞化学）和神经肌肉功能 （电生理学）。 雌激素和雄激素的协同作用， 雌激素可用性的必要性，脊髓上和局部的作用 神经元间的、雌激素敏感的传入神经，以及自然的影响 将评估形态发育中出现的雌激素水平。 因为芳香酶的瞬时表达已被报道在多种 为了发育神经结构，产后脊髓将被检测 芳香酶的存在。 雌激素的调节作用 这些运动神经元中常见的间隙连接的发展将 也予以检查。 发育过程中运动神经元兴奋性的变化是 可能负责脊髓介导的反射的发生，以及作用 雌激素和雄激素在多种功能特性发展中的作用 将评估这些激素敏感运动神经元的数量。 因为最近 有证据表明雌激素实际上与脊髓有关 男性化，这些研究可能有助于统一我们对男性化的理解 发育中的哺乳动物中枢的性别分化过程 神经系统。