HORMONAL REGULATION OF BRAIN AND BEHAVIOR DEVELOPMENT

这个项目旨在研究类固醇激素的作用， 尤其是雌激素，在大脑和行为的发育中。 目前，大脑和行为的性别分化的两种模型是 被认为存在的。在哺乳动物中，来源于睾丸的雌激素 雄激素，被认为导致神经解剖学的男性发育和 性行为。在鸟类中，雌激素由细胞直接分泌 女性卵巢被认为会导致女性交配的发育 行为。与这种更典型的鸟类有性繁殖模式不同 分化，斑雀的神经鸣叫控制系统( 会唱歌的雄性比不会唱歌的雌性要大得多) 效仿哺乳动物的模式，在…的影响下男性化 雌二醇来源于男性睾丸分泌的雄激素。主 支持这一理论的数据是，对患有 孵化后头几周的雌激素会导致阳性 发展他们的神经歌曲系统，并允许他们在 成人期。然而，各种实验都与 从睾丸分泌物中提取的雌激素通常是 促进男性发育的物质。目前，它 目前尚不清楚歌曲系统通常是如何进行性别区分的。这 该提案旨在检验两个假设：(I)斑马雀鸣叫 系统类似于鸟类的交配系统，因为它是 男性化不是由于睾丸中的类固醇的存在，而是 由于缺乏雌二醇和/或其他卵巢因子，以及(Ii) 斑马雀的鸣唱系统类似于斑马雀的交配系统 哺乳动物的雄性化是在雌二醇的影响下发生的， 无论是直接还是间接。这些实验旨在测试如何 卵巢和睾丸组织，分开和协调，影响 斑马鸣叫和交配系统的性别分化 是雀类。再远一点。这项研究将调查其潜在的作用 雌激素和神经生长因子受体与脑发育 和行为。胚胎斑马雀将被用一种抑制剂治疗 雌激素合成或雌激素，以确定对歌曲的影响 和交配系统(I)雌激素水平的这种变化，以及 (Ii)遗传女性的睾丸组织(雌激素的合成 抑制物诱导)和遗传男性的卵巢组织(其中雌二醇 归纳)。然后，将在整个大脑中检测雌激素受体 处于不同的发育阶段。最后，神经上的性别差异 生长因子结合将在整个开发过程中进行调查，并 控制雌激素水平对结合力影响 将对性别分化时期进行研究。

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.