The Cerebral Cortex as a Target of Estrogen and the Neurotrophins

大脑皮层作为雌激素和神经营养素的靶点

• 批准号: 9602029
• 负责人: C. Dominique Toran-Allerand
• 金额: $ 21.6万
• 依托单位: Columbia University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-08-01 至 2000-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9602029&HistoricalAwards=false
• 关键词: Cerebral; Cortex; Target; Estrogen; Neurotrophins

9602029 Toran-Allerand The gonadal steroid, estrogen, has multiple effects on the brain. One of its well characterized actions is to regulate the activity of the reproductive axis. However, an additional action of perhaps even greater consequence, is to influence the growth and differentiation of neurons in the brain. Recently published studies by Dr. Toran-Allerand revealed that estrogens may be intimately involved in modulating growth factor production in the brain forming the basis for estrogen's growth modulating effects but ultimately, estrogen also alters cognitive function. Dr. Toran-Allerand is continuing to investigate the interplay between estrogen and growth factors by studying the signal transduction pathways elicited by receptor stimulation. In exciting preliminary results, evidence for receptor cross-talk has been found. These studies are continuing and have been enhanced by investigations to analyze key elements of the estrogen and growth factor systems, including receptor coupling and protein kinases. That estrogen interacts in neurons with growth factors and their receptors introduces an important new regulatory system with implications for the development of the neuronal targets of estrogen. Although sex differences in circulating estrogen and androgen levels during early life represent an important epigenetic influence and appear to play a crucial role, it remains to be determined precisely how exposure to circulating masculine and feminine gonadal steroid hormone levels are translated into permanent differentiation of the neural circuitry supporting sexually dimorphic behavioral patterns. By stimulating the synthesis of proteins required for neuronal differentiation, survival and maintenance of function, estrogen and growth factors, acting perhaps in concert, as well as reciprocally, may have important and intertwined developmental roles. Thus, mediation of estrogen action by interactions with locally synthesized growth factors an d their receptors may represent a universal mechanism by which the effects of hormones, such as estrogen, may exert local control and exhibit both tissue and developmental specificity's. These studies essentially provide the biological basis for gender differences in behavior among all animal species, including man.

性腺类固醇，雌激素，对大脑有多种影响。它的一个特点是调节生殖轴的活动。然而，另一个可能更重要的作用是影响大脑中神经元的生长和分化。Toran-Allerand博士最近发表的研究表明，雌激素可能密切参与调节大脑中生长因子的产生，形成了雌激素调节生长作用的基础，但最终，雌激素也会改变认知功能。Toran-Allerand博士通过研究受体刺激引发的信号转导途径，继续研究雌激素与生长因子之间的相互作用。在令人兴奋的初步结果中，发现了受体串扰的证据。这些研究仍在继续，并通过调查分析雌激素和生长因子系统的关键要素，包括受体偶联和蛋白激酶，加强了这些研究。雌激素在神经元中与生长因子及其受体的相互作用引入了一个重要的新调控系统，对雌激素的神经元靶点的发育具有重要意义。尽管生命早期循环雌激素和雄激素水平的性别差异代表了重要的表观遗传影响，似乎起着至关重要的作用，但仍有待确定的是，暴露于循环男性和女性性腺类固醇激素水平是如何转化为支持两性二态行为模式的神经回路的永久分化的。通过刺激神经元分化、存活和维持功能所需的蛋白质合成，雌激素和生长因子可能协同作用，也可能相互作用，可能具有重要的相互交织的发育作用。因此，通过与局部合成的生长因子及其受体的相互作用介导雌激素的作用可能代表了一种普遍的机制，通过这种机制，激素（如雌激素）可能发挥局部控制作用，并表现出组织和发育特异性。这些研究基本上为包括人类在内的所有动物物种在行为上的性别差异提供了生物学基础。