MECHANISMS OF HORMONAL CONTROL OF NEURAL DEVELOPMENT

大鼠的大脑在形态上有显著的性别差异： 视前区的性二形核(SDN-POA)，它是 雄性大鼠比雌性大鼠大几倍。这一区域的神经元 在发育过程中结合高水平的类固醇，以及 此时细胞核似乎是由荷尔蒙环境决定的。 因为SDN-POA中的性别差异是如此显著，而且因为它 可以在发育过程中通过激素治疗来操纵，它提供了 有机会研究大脑发育的基本机制 以及它的性别分化。拟议研究的目的是 调查SND-POA是相互关联的 性二态神经系统，以及该系统各组成部分发挥作用 在发育过程中营养相互影响。具体地说，三个 将进行分组研究。第一组将使用程序 类似于以前对SDN-POA的研究中使用的那些，以识别和 量化大脑其他类固醇结合区域的性别差异，以及 描述这些性别差异发展的时间进程。 第二组研究将使用顺行和逆行 轨迹跟踪技术，以确定可能的投影之间的 SDN-POA和其他与类固醇结合的神经区域。第三组 研究将使用病变和类固醇植入物来调查 有可能这些投影是区分 SDN-POA，以及参与性别分化的一种机制 大脑是类固醇相关的、跨突触的神经元增强 生死存亡。这些研究将有助于阐明涉及的机制 发育出一种特定的神经性别差异，即SDN-POA。此外, 所获得的信息应证明与我们对 一般情况下，神经组织和发展的潜在机制。这 了解有助于预防或改善神经性疾病 精神错乱。拟议的研究还可提供与以下方面有关的信息 孕期激素暴露的发育后果。

There is a marked morphological sex difference in the brain of the rat: the sexually dimorphic nucleus of the preoptic area (SDN-POA), which is several-fold larger in male than in female rats. Neurons in this region bind high levels of steroids during development, and the size of the nucleus appears to be determined by the hormonal environment at this time. Because the sex difference in the SDN-POA is so dramatic, and because it can be manipulated by hormonal treatments during development, it provides an opportunity to study the basic mechanisms underlying brain development and its sexual differentiation. The aim of the proposed research is to investigate the possibility that the SND-POA is part of an interrelated sexually dimorphic neural system, and that components of this system exert trophic influences on one another during development. Specifically, three groups of studies will be conducted. The first group will use procedures similar to those used in previous studies of the SDN-POA, to identify and quantify sex differences in other steroid-binding regions of the brain, and to describe the time course for the development of these sex differences. The second group of studies will use anterograde an retrograde tract-tracing techniques to identify possible projections between the SDN-POA and other neural regions that bind steroids. The third group of studies will use lesions and steroid implants to investigate the possibility that these projections are necessary for differentiation of the SDN-POA, and that one mechanism involved in sexual differentiation of the brain is a steroid-related, transsynaptic potentiation of neuronal survival. These studies will help elucidate the mechanisms involved in development of a specific neural sex difference, the SDN-POA. In addition, the information gained should prove relevant to our understanding of mechanisms underlying neural organization and development in general. This understanding could aid in prevention or amelioration of neurological disorders. The proposed research may also provide information related to the developmental consequences of hormone exposure during pregnancy.