Neuroendocrine Regulation of Behavior

描述(申请人提供)：卵巢类固醇激素的许多神经内分泌和行为影响是通过类固醇受体作为神经元的基因调节器来调节的。然而，除了受激素调节外，激素受体神经元也是神经元网络的一部分，因此受到来自其他神经解剖学领域和环境来源的传入输入的影响。在某些情况下，这些传入影响调节受体的浓度，改变随后对激素的敏感性；在其他情况下，传入影响通过被称为配体非依赖性激活的过程激活受体，导致类固醇受体依赖的神经元反应的修饰。将使用一个模型，在该模型中，生殖器感觉刺激通过激活神经元孕酮受体来增强生殖行为的表达。关于神经解剖位置和细胞过程的假设，社会环境来源的传入输入通过这些输入影响含有孕激素受体的神经元的功能，将被测试。离散的神经解剖区域将被识别，这些区域对于传递这种传入信息是必不可少的，导致孕激素受体依赖、配体非依赖、神经元和行为的改变。然后将确定所涉及的多巴胺能细胞群。这一假设将得到检验，即生殖感觉刺激通过与D1多巴胺受体刺激相同的孕激素受体依赖的细胞内机制来诱导一些神经元和行为变化。这项研究的长期目标是了解社会环境通过神经递质影响神经元类固醇激素受体以调节行为和其他神经内分泌事件的过程。由于类固醇激素和多巴胺在某些情感障碍的病因和治疗中的重要性，研究多巴胺和环境刺激对类固醇激素受体的影响可能对人类健康具有重要意义。

DESCRIPTION (provided by applicant): Many neuroendocrine and behavioral effects of ovarian steroid hormones are mediated by steroid receptors acting as gene regulators in neurons. However, besides being regulated by the hormones, hormone-receptor-containing neurons are part of neuronal networks, and therefore are influenced by afferent input from other neuroanatomical areas and environmental sources. In some cases, these afferent influences modulate the concentration of receptors, changing subsequent sensitivity to hormones; in other cases the afferent influences activate the receptors by a process known as ligand-independent activation, resulting in steroid receptor-dependent modification of neuronal responses. A model will be used in which genitosensory stimulation enhances the expression of reproductive behaviors by activation of neuronal progesterone receptors. Hypotheses concerning the neuroanatomical sites and cellular processes by which afferent input from social environmental sources influences the function of the progesterone receptor-containing neurons will be tested. Discrete neuroanatomical areas will be identified that are essential for transduction of this afferent information, resulting in progesterone receptor-dependent, ligand-independent, neuronal and behavioral changes. Then the dopaminergic cell groups involved will be determined. The hypothesis will be tested that genitosensory stimulation induces some neuronal and behavioral changes by the same progesterone-receptor-dependent, intracellular mechanism that D1 dopamine receptor stimulation does. The long-range goal of this research is to understand the processes by which the social environment, acting via neurotransmitters, influences neuronal, steroid hormone receptors to modulate the expression of behaviors and other neuroendocrine events. Because of the importance of steroid hormones and dopamine in the etiology and treatment of some affective disorders, the study of the influences of dopamine and environmental stimulation on steroid hormone receptors may be of great relevance to human health.