HORMONAL REGULATION OF BRAIN AND BEHAVIOR DEVELOPMENT

大脑荷尔蒙调节和行为发展

基本信息

批准号：
6186276
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
项目类别：
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

项目摘要

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，对大脑和行为的发育有影响。目前，大脑和行为的性别分化有两种模型：认为存在。在哺乳动物中，雌激素来自睾丸雄激素，被认为会导致神经解剖学的男性发育和性行为。在鸟类中，雌激素是由女性卵巢被认为是导致女性交配发育的原因行为。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（人们认为，唱歌的雄性比不唱歌的雌性大得多）遵循哺乳动物的模式并在雌二醇源自男性睾丸分泌的雄激素。主要支持该理论的数据是，对女性进行治疗孵化后最初几周内的雌激素会导致雄性化开发他们的神经歌曲系统并让他们唱歌成年期。然而，各种实验都与此不相容。认为雌激素通常来自睾丸分泌物促进男性男性发育的物质。目前，它目前尚不清楚歌曲系统通常如何进行性别区分。这该提案旨在测试两个假设：（i）斑胸草雀的鸣叫该系统与鸟类的交配系统相似，男性化不是因为睾丸中存在类固醇，而是由于缺乏雌二醇和/或其他卵巢因子，以及 (ii) 斑胸草雀的鸣叫系统与雀科雀的交配系统相似哺乳动物的男性化是在雌二醇的影响下发生的，直接或间接。这些实验旨在测试如何卵巢和睾丸组织分别和共同影响斑马鸣叫和交配系统的性别分化雀类。更远。这些研究将调查潜在的作用雌激素和神经生长因子受体在大脑发育中的作用和行为。胚胎斑胸草雀将接受抑制剂治疗雌激素合成或雌激素以确定对歌曲的影响和（i）雌激素水平的这种改变的交配系统，以及 (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（其中雌二醇诱导）。然后，将在整个大脑中检测雌激素受体处于不同的发展阶段。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，并且期间控制雌激素水平对结合的影响将研究性别分化时期。