ONTOGENY OF ESTROGEN TARGET NEURONS IN THE FOREBRAIN

众所周知，雌激素在塑造发育中的 神经系统 这项研究的最终目标是了解 雌激素对哺乳动物大脑发育的深远影响。 围产期雌激素暴露，来自于 循环的睾丸激素，使形态永久男性化， 连接性和中枢神经许多区域的化学 系统 许多行为和生理功能也永久地 获得男性典型的模式，以应对围产期雌激素。 的 雌激素在发育过程中最显著的作用发生在神经回路中 在成年人中，含有雌激素靶细胞， 生殖行为和生理学。 激素分泌异常或 发育早期的神经传递可能影响雌激素诱导的 大脑的分化，可能会破坏神经控制， 生殖或其他大脑功能。 雌激素与雌激素特异性受体结合， 重要的是改变蛋白质合成。 假设是， 这项研究的核心是， 发育中的大脑中的神经元接受并吸收雌激素 信号等对雌激素诱导分化至关重要。 的 进行的实验将确定何时含有雌激素受体的 当神经元开始表达功能性雌激素时， 受体，无论它们是否受到选择性细胞死亡， 是否存在雌激素，以及是否选择突触和 激素信号相互作用，影响雌激素目标的存活 神经元 分析将首先集中于 雌激素靶细胞在大鼠视前区。 这种生殖性 相关的大脑区域都有记录。依赖于性别的差异 形态学和受体分布。 组织化学技术检测 雌激素受体，出生日期标记，细胞死亡标记，发展 神经连接和其他神经元分化的标志物， 用于鉴定选择的雌激素受体表达亚群， 从早期胚胎阶段到成年期的细胞。

Estrogen is known to play a fundamental role in sculpting the developing nervous system. The ultimate goal of this research will be to understand the profound impact of estrogen on the developing mammalian brain. Perinatal estrogen exposure, derived from estrogenic metabolites of circulating testosterone, permanently masculinizes the morphology, connectivity, and chemistry of many regions of the central nervous system. Many behaviors and physiological functions also permanently acquire a male-typical pattern in response to perinatal estrogen. The most dramatic effects of estrogen in development occur in neural circuits that, in the adult, contain estrogen target cells and participate in reproductive behavior and physiology. Abnormal hormone secretion or neurotransmission during early development may affect estrogen-induced differentiation of the brain, possibly disrupting neural control of reproduction or other brain functions. Estrogen binds to estrogen-specific receptors that act as transcription factors, importantly altering protein synthesis. The hypothesis that is central to the proposed studies is that estrogen receptor-containing neurons in the developing brain receive and transduce the estrogenic signal and so are crucial to estrogen-induced differentiation. The experiments performed will determine when estrogen receptor-containing neurons are born, when they begin to express functional estrogen receptor, whether they are subject to selective cell death in the presence or absence of estrogen, and whether selected synaptic and hormonal signals interact to affect the survival of estrogen target neurons. The analyses will initially concentrate on the development of estrogen target cells in the rat preoptic area. This reproductively relevant brain region has documented. hormone-dependent differences in morphology and receptor distribution. Histochemical techniques to detect estrogen receptors, birthdate markers, cell death markers, developing neural connections, and other markers of neuronal differentiation will be employed to identify selected subsets of estrogen receptor-expressing cells from early embryonic stages through adulthood.