The Cerebral Cortex as a Target of Estrogen and the Neurotrophins

9602029 Toran-Allerand性腺类固醇雌激素对大脑有多种影响。它的特征之一就是调节生殖轴的活动。然而，另一个可能产生更大后果的行动，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，形成雌激素生长调节作用的基础，但最终，雌激素也会改变认知功能。Toran-Allerand博士正在继续通过研究受体刺激引发的信号转导途径来研究雌激素和生长因子之间的相互作用。在令人兴奋的初步结果中，已经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元素，包括受体偶联和蛋白激酶，得到了加强。雌激素在神经元中与生长因子及其受体相互作用，引入了一个重要的新调节系统，对雌激素神经元靶点的发育具有重要意义。尽管早期生命中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，并似乎发挥了关键作用，但仍未确切确定，暴露于循环中的男性和女性性腺类固醇激素水平如何转化为支持性二态行为模式的神经回路的永久分化。通过刺激神经元分化、生存和维持功能所需的蛋白质的合成，雌激素和生长因子可能协同作用，也可能相互作用，可能具有重要的和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来调节雌激素的作用，可能代表了一种普遍的机制，通过这种机制，雌激素等激素的作用可能发挥局部调控作用，并显示出组织和发育的特异性。这些研究基本上为包括人类在内的所有动物物种的行为性别差异提供了生物学基础。

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.