Gonadal Hormone Influences on Brain Activity

在雌性大鼠中，性腺激素雌激素和孕激素调节大脑中神经递质多巴胺（DA）的活性。 本实验室的实验旨在确定调节雌激素在大脑中作用的机制，并试图确定这种现象在大鼠自然行为中的功能作用。 考虑到后者，我们发现DA在大脑的一个特定区域，纹状体，是重要的雌性大鼠生殖行为的特定方面。 介导性腺激素对纹状体的作用的机制似乎与介导雌激素和孕激素对细胞内（传统）雌激素受体的作用的机制不同。 我实验室的研究一再证明，雌激素通过一种新的机制作用于纹状体。 关于性腺激素在调节雌性大鼠DA活性中的作用，本实验将解决两个关键问题：1）雌激素对纹状体作用的介导机制是什么？纹状体和DA释放在雌性大鼠生殖行为中的作用是什么？性腺类固醇激素参与纹状体DA活性的调节对于我们理解神经内分泌学的基本过程以及我们理解基底神经节的功能是重要的。 确定类固醇激素在大脑中作用的新机制对我们了解这些激素在何处，如何以及何时影响大脑活动和行为具有重要意义。 最后，这些实验将帮助我们了解这些激素如何调节雌性大鼠的行为。

In female rats, the gonadal hormones estrogen and progesterone modulate activity of the neurotransmitter, dopamine (DA), in the brain. Experiments in this laboratory have been directed at defining the mechanisms mediating the effect of estrogen in the brain, as well as attempting to determine the functional role of this phenomena in the natural behavior of the rat. With the latter in mind, we find that DA in one particular area of the brain, the striatum, is important for specific aspects of the female rat reproductive behavior. The mechanism(s) mediating the effects of the gonadal hormones on the striatum appears to be different from those mediating the effects of estrogen and progesterone at intracellular (traditional) estrogen receptors. Research from my laboratory has repeatedly demonstrated that estrogen acts in the striatum through a novel mechanism. There are two key questions about the role of gonadal hormones in the modulation of DA activity in the female rat that the experiments in this proposal will address: 1) What are the mechanism(s) mediating the effects of estrogen on the striatum?; and 2) What role(s) of the striatum, and of DA release, in reproductive behavior in the female rat?The involvement of the gonadal steroid hormones in the modulation of striatal DA activity is important for our understanding of the basic processes of neuroendocrinology as well as our understanding of the functions of the basal ganglia. Identifying novel mechanisms through which steroid hormones act in the brain has important implications for our understanding of where, how, and when these hormones affect the brain activity and behavior. Finally, these experiments will help us to understand how these hormones modulate behavior in the female rat.