FUNCTION OF GNRH IN NASAL GLANDS

描述：（改编自研究者摘要）神经元含有 性激素，促性腺激素释放激素（GnRH），在鼻腔中发现， 沿着终神经的腔沿着。PI有初步证据表明， 终神经分泌GnRH进入鼻腔以调节化学感受性 转导过程。在人类中，GnRH鼻喷雾剂正在测试治疗 许多疾病和病症，包括癌症、子宫内膜异位症和 不孕这些治疗对化学感受的可能副作用有 未被确认。为矫正结构缺陷而进行的鼻部手术 可能会破坏含GnRH的神经。干预的临床意义 与GnRH投射到鼻结构的关系尚不清楚。更好的基础 了解GnRH在鼻腔中的功能，我们可以更好地预测 这些临床操作中的一些可能影响化学感觉功能和/或 其对生殖的影响。 本研究的长期目标是：1）了解GnRH如何 与鼻腔化学感觉系统相互作用，2）了解是什么因素导致 鼻内GnRH释放，和3）确定的临床意义 干扰鼻腔GnRH系统这项研究计划的主要目标是 在鼻腔中识别GnRH进入鼻腔的途径， 受体。 PI的初步证据表明，GnRH受体存在于 化学感受神经元的树突。然而，神经的GnRH过程 终板仅延伸到固有层中。紧密连接将 从下面的固有层上皮的表面，它是 GnRH不太可能扩散到上皮表面。的机制 哪个GnRH进入嗅觉树突上的GnRH受体 将由这项研究决定。私家侦探的初步证据显示 GnRH通过鼻腺的粘液到达化学感受树突。 哺乳动物和两栖动物的鼻腺及其上覆的粘液， GnRH免疫阳性无论是鼻腺细胞合成GnRH还是摄取 将通过原位试验检测来自局部终神经纤维的GnRH 杂交和定量放射自显影， 外源性GnRH。将进行药理学实验， 用定量放射自显影研究鼻腺的GnRH释放 组织和孵育溶液的放射性测定。这些实验将 为嗅觉的激素调节提供了新的见解。

DESCRIPTION: (Adapted from the Investigator's Abstract) Neurons containing the sex hormone, gonadotropin-releasing hormone (GnRH), are found in the nasal cavity along the nervus terminalis. The PI has preliminary evidence that the nervus terminalis secretes GnRH into the nasal cavity to modulate chemosensory transduction processes. In humans, GnRH nasal sprays are being tested to treat a number of diseases and disorders including cancers, endometriosis, and infertility. Possible side effects of these treatments on chemoreception have not been identified. Nasal surgeries performed to correct structural defects may disrupt the GnRH-containing nerve. The clinical significance of interfering with GnRH projections to nasal structures is not known. With a better basic understanding of GnRH function in the nasal cavity, we can better predict how some of these clinical manipulations may affect chemosensory functioning and/or its consequential effects on reproduction. The long-term objectives of this research are to 1) understand how GnRH interacts with the nasal chemosensory systems, 2) understand what factors cause intranasal GnRH release, and 3) determine the clinical significance of interfering with the nasal GnRH system. The main goal of this research proposal is to identify, in the nasal cavity, the route by which GnRH accesses the GnRH receptors. The PI's preliminary evidence suggests that GnRH receptors exist on the dendrites of chemoreceptive neurons. However, the GnRH processes of the nervus terminalis extend only into the lamina propria. With tight junctions separating the surface of the epithelium from the underlying lamina propria, it is unlikely that GnRH diffuses to the surface of the epithelium. The mechanism by which GnRH accesses the GnRH receptors on the olfactory dendritic processes will be determined by this research. The PI's preliminary evidence suggests that GnRH accesses the chemosensory dendrites via mucous from nasal glands. Nasal glands and the overlying mucous in mammals and amphibians are immunopositive for GnRH. Whether nasal gland cells synthesize GnRH or take up GnRH from local nervus terminalis fibers will be tested by performing in situ hybridization, and quantitative autoradiography following incubation in exogenous GnRH, respectively. Pharmacological experiments will be performed to study GnRH release from nasal glands using quantitative autoradiography of the tissue and radioassays of the incubating solutions. These experiments will provide the field with new insight into hormonal modulation of olfaction.