HORMONAL REGULATION OF BRAIN AND BEHAVIOR DEVELOPMENT

大脑荷尔蒙调节和行为发展

• 批准号: 2675459
• 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/2675459
• 关键词: 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; songbirds; 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， 特别是雌激素，在大脑和行为的发展中。 目前，大脑和行为性别分化的两种模型是： 认为存在。在哺乳动物中，来自睾丸的雌激素 雄激素，被认为是导致神经解剖学的男性化发展， 性行为在鸟类中，雌激素是由 雌性卵巢被认为是导致雌性交配的原因 行为。与这种更典型的鸟类性行为模式不同， 分化，斑胸草雀的神经歌曲控制系统（ 会唱歌的雄性比不唱歌的雌性大得多） 遵循哺乳动物的模式，在 由男性睾丸分泌的雄激素衍生的雌二醇。主要 支持这一理论的数据是， 雌激素在孵化后的头几周会导致雄性 发展他们的神经歌唱系统，让他们唱歌， 成年然而，各种各样的实验都不符合 睾丸分泌物中的雌激素通常是 促进男性发展的物质。目前已 目前还不清楚鸣唱系统在正常情况下是如何区分性别的。这 建议是为了测试两个假设：（一）斑马雀的歌声 系统与鸟类的交配系统相似，因为它是 不是因为睾丸中的类固醇而雄性化， 通过缺乏雌二醇和/或其他卵巢因子，和（ii） 斑胸草雀的鸣唱系统类似于 哺乳动物的雄性化在雌二醇的影响下发生， 直接或间接地。这些实验旨在测试 卵巢和睾丸组织，单独或共同影响 斑马鸣唱和交配系统的性别分化 雀类。进一步.这些研究将调查以下因素的潜在作用： 雌激素和神经生长因子受体与脑发育 和行为。斑胸草雀的胚胎会被注射一种抑制剂 雌激素合成或雌激素来确定对歌曲的影响 和交配系统（i）雌激素水平的这种改变，和 (ii)遗传女性的睾丸组织（雌激素合成 抑制剂诱导）和遗传男性的卵巢组织（ 诱导）。然后，雌激素受体将在整个大脑中进行检测， 在不同的发展阶段。最后，神经的性别差异 将在整个开发过程中研究生长因子结合， 控制雌激素水平对结合影响 性分化期进行研究。