HORMONAL REGULATION OF BRAIN AND BEHAVIOR DEVELOPMENT

大脑荷尔蒙调节和行为发展

• 批准号: 2431000
• 负责人: JULI S. WADE
• 金额: $ 10.29万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-06-01 至 2001-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2431000
• 关键词: Aves; androgen receptor; animal communication behavior; animal developmental psychology; aromatase; autoradiography; behavioral /social science research tag; developmental neurobiology; estradiol; estrogen inhibitor; estrogen receptors; estrogens; female; hormone regulation /control mechanism; male; neurotrophic factors; nonmammalian vertebrate embryology; ovary; receptor binding; sex behavior; sex differentiation; telencephalon; testis; testosterone

This project is designed to investigate the role of steroid hormones, estrogen in particular, in the development of brain and behavior. Currently, two models of sexual differentiation of brain and behavior are thought to exist. In mammals, estrogen, derived from testicular androgens, is thought to cause masculine development of neuroanatomy and sexual behaviors. in birds, estrogen that is secreted directly by the female ovary is thought to cause feminine development of copulatory behaviors. Unlike this more typical pattern of avian sexual differentiation, the neural song control system of zebra finches (which is much larger in males that sing than in females that do not) is thought to follow the mammalian pattern and masculinize under the influence of estradiol derived from androgen secreted by the testes in males. The main data in support of that theory are that treatment of females with estrogen in the first few weeks after hatching will cause masculine development of their neural song systems and allow them to sing in adulthood. However, a variety of experiments are incompatible with the idea that estrogen derived from testicular secretions is normally the substance that promotes masculine development in males. At present, it is unclear how the song system normally sexually differentiates. This proposal is designed to test two hypotheses: (i) the zebra finch song system is similar to the copulatory system of birds in that it is masculinized not by the presence of steroids derived form the testes but by the absence of estradiol and/or other ovarian factors, and (ii) the song system of zebra finches is similar to the copulatory system of mammals in that masculinization occurs under the influence of estradiol, either directly or indirectly. The experiments are designed to test how ovarian and testicular tissue, separately and in concert, influence sexual differentiation of the song and copulatory systems in zebra finches. Further. the studies will investigate the potential roles of estrogen and nerve growth factor receptors in the development of brain and behavior. Embryonic zebra finches will be treated with an inhibitor of estrogen synthesis or estrogen to determine the effects on the song and copulatory systems of (i) such alterations in estrogen levels, and (ii) testicular tissue in genetic females (which the estrogen synthesis inhibitor induces) and ovarian tissue in genetic males (which estradiol induces). Then, estrogen receptors will be assayed throughout the brain at a variety of developmental stages. Finally, sex differences in nerve growth factor binding will be investigated throughout development, and the effect on that binding of manipulating estrogen levels during the period of sexual differentiation will be studied.

该项目旨在研究类固醇激素的作用， 尤其是雌激素，在大脑和行为的发展中。 目前，大脑和行为的两种性别差异模型是 被认为存在。在哺乳动物中，雌激素源自睾丸 雄激素被认为会导致神经解剖学和 性行为。在鸟类中，直接由 人们认为女性卵巢会导致女性发展的女性发展 行为。与这种更典型的鸟类性模式不同 分化，斑马雀科的神经歌曲控制系统（它 在唱歌的男性中比女性大得多）被认为 遵循哺乳动物模式并在 雌激素衍生自男性睾丸分泌的雌激素。主 支持该理论的数据是对女性的治疗 孵化后的头几周雌激素会导致男性 开发他们的神经歌曲系统，让他们唱歌 成年。但是，各种实验与 源自睾丸分泌的雌激素的想法通常是 促进男性男性发展的物质。目前，它 尚不清楚歌曲系统通常如何进行性别区分。这 建议旨在检验两个假设：（i）斑马雀科歌曲 系统类似于鸟类的交配系统 睾丸的类固醇的存在不是由男性化的，而是 由于没有雌二醇和/或其他卵巢因素，以及（ii） 斑马雀的歌曲系统类似于交配系统 哺乳动物是男性化的，发生在雌二醇的影响下 直接或间接。实验旨在测试如何 卵巢和睾丸组织分别且协同影响 斑马的歌曲和交配系统的性差异化 雀科。更远。研究将研究 雌激素和神经生长因子受体在大脑的发展中 和行为。胚胎斑马雀将用抑制剂治疗 雌激素合成或雌激素以确定对歌曲的影响 以及（i）雌激素水平的这种改变的系统，以及 （ii）遗传雌性合成的遗传组织 抑制剂诱导）和卵巢组织在遗传雄性中（雌二醇 诱导）。然后，将在整个大脑中分析雌激素受体 在各种发展阶段。最后，神经的性别差异 生长因子结合将在整个开发过程中进行研究，并且 对操纵雌激素水平的结合的影响 将研究性别差异的时期。