RUI: Gonadotropin Hormone-Releasing Hormone Systems

9308452 Demski促性腺激素释放激素(GnRH)是1971年从脑中分离得到的一种十肽。这种激素是从前基底前脑的神经元释放出来的，这些神经元通过下丘脑腹侧投射到正中隆起，作用于垂体，调节黄体生成素和卵泡刺激素的控制。因此，GnRH在排卵和睾酮的产生中起着关键作用。然而，随着敏感和特异抗体技术的发展，现在已经清楚地表明，GnRH神经元网络是一个复杂的、异质的系统，由三个或更多离散的神经元群组成，横跨大脑中非常不同的区域。除了下丘脑区，这些肽还产生于末梢神经节和动眼神经复合体附近的中脑被盖的细胞中。人们对这两个神经系统可能扮演的生理角色知之甚少。利用最先进的神经解剖学技术，德姆斯基博士和他的本科生将绘制出GnRH系统在这些大脑区域的功能连接图。他们将对发育中的大脑进行详细的解剖学检查。一种特殊的逆行神经示踪剂将用于识别含有GnRH的神经元和脑血管之间的细胞连接。此外，德姆斯基博士将在发育的不同阶段损伤末梢神经，并确定对生理和特定行为发育的影响。这一结果将为了解位于内分泌下丘脑之外的促性腺激素释放激素系统的组织、功能和作用机制提供新的见解。此外，人类的许多生殖功能障碍都是由于促性腺激素释放激素系统的紊乱造成的。例如，Kallman综合征，一种以不育和嗅觉障碍为特征的先天性疾病，由GnRH神经元迁移缺陷引起，性腺功能低下，特征是青春期延迟和不育，由Gn RH缺乏引起。从这项工作中获得的基本信息可能有助于为GnRH功能障碍患者开发有效的治疗方法。***

9308452 Demski Gonadotropin-releasing hormone (GnRH) is a decapeptide that was isolated from brain in 1971. This hormone is released from neurons of the anterior basal forebrain which project through the ventral hypothalamus to the median eminence and act upon the pituitary to regulate the control of luteinizing hormone and follicle stimulating hormones. Thus, GnRH plays a pivotal role in ovulation and testosterone production. However, with the development of sensitive and specific antibody techniques, it has now become clear that GnRH neuronal network is a complex, heterogenous system, comprising three or more discrete neuronal groups and spanning vastly different regions of the brain. Besides the hypothalamic area, the peptides are produced in cells in the terminal nerve ganglia and the midbrain tegmentum near the oculomotor complex. Little is known of the physiological roles that these two other neuronal systems may play. Using state-of- the-art neuroanatomical techniques, Dr. Demski and his undergraduate students will map the functional connections of GnRH system in these brain regions. They will provide a detailed anatomical examination of developing brains. A special retrograde neural tracer will be used to identify cellular connections between GnRH-containing neurons and cerebral blood vessels. In addition, Dr. Demski will lesion the terminal nerve at different stages of development and determine the effects on the physiology and development of specific behaviors. The results should provide new insights into the organization, function and mechanisms of action of the GnRH systems lying outside the endocrine hypothalamus. Moreover, many reproductive dysfunctions in humans result from a disorder in the GnRH system. For example, Kallman's Syndrome, a congenital disorder characterized by sterility and anosmia, is caused by a defect in the migration of GnRH neurons and hypogonadism, characterized by delayed puberty and sterility, results from Gn RH deficiency. Fundamental information gained from this work may help facilitate the development of effective treatments for patients suffering from GnRH dysfunctions. ***