SGER: Ontogeny of GnRH Expression Vertebrate Neurons

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。随着先进抗体技术的发展，促性腺激素释放激素神经网络被证明是一个复杂的、异质的系统，由三个或多个离散的神经元群组成，跨越大脑的不同区域，包括嗅球和神经内的终末神经节，包括视前区的基底前脑，以及尾侧间脑或中脑区域。此外，促性腺激素释放激素神经元投射到大脑内外的靶点，既是一种激素，也是一种神经递质。它与控制神经内分泌学特征的表达和维持有关，这些特征是行为生殖机制的基础。授予巴斯博士的这一小额探索性研究奖将促进敏感和特定的分子工具的开发，这些工具将有助于为大脑和行为的性别分化的荷尔蒙控制提供新的细胞和分子基础。他将在一个特定物种中完成GnRH基因的序列分析和序列比较，该物种作为研究大脑和行为中性二态的模型。巴斯博士将使用克隆的cDNA产生的反义核糖核酸转录本和原位杂交组织化学来鉴定新的GnRH转录本在具有不同生殖表型的幼年和成年动物的大脑中的表达模式和数量水平。这些新的灵敏分子工具的开发将为这一新兴研究领域开辟新的途径。这项研究将有助于更好地理解GnRH在生殖成熟的基本机制、生理和物种典型行为中所起的作用。

Gonadotropin-releasing hormone (GnRH) is a decapeptide that was isolated from brain in 1971. With the development of sophisticated antibody technology, the GnRH neuronal network was demonstrated to be a complex, heterogenous system, comprising three or more discrete neuronal groups and spanning vastly different regions of the brain, including the ganglion of the terminal nerve within the olfactory bulb and nerve, the basal forebrain including the preoptic area, and the caudal diencephalon or midbrain region. Moreover, GnRH neurons project to targets within and outside the brain and serves as both a hormone and a neurotransmitter. It is implicated in controlling the expression and maintenance of neuroendocrinological traits underlying behavioral reproductive mechanisms. This Small Grant for Exploratory Research award to Dr. Bass will facilitate the development of sensitive and specific molecular tools which will be instrumental in providing new insights into the cellular and molecular bases for hormonal control of sexual differentiation of brain and behavior. He will complete the sequence analysis and sequence comparisons of cDNAs for GnRH in a specific species that serves as a model to examine intrasexual dimorphisms in brain and behavior. Dr. Bass will use the antisense ribonucleic acid transcripts generated from the cloned cDNAs and in situ hybridization histochemistry to identify the expression patterns and quantitate levels of novel GnRH transcripts in the brain of juvenile and adult animals with distinct reproductive phenotypes. The development of these new sensitive molecular tools will open up new avenues into this emerging research area. The research will lead to a better understanding of the role that GnRH plays in basic mechanisms underlying reproducive maturation, physiology and species-typical behaviors.