Regulation of Gonadotropin Expression by GnRH Pulses

描述（由申请人提供）： 促性腺激素释放激素（GnRH）是生殖的关键调节因子。 促卵泡激素（FSH）和促黄体生成激素（LH）是不同的 由GnRH的不同脉冲频率调节。这项提案的目的是 确定LH和FSH基因表达的调节机制， 脉动性GnRH 具体目标1：确定脉冲频率 确定导致LH β最大表达的GnRH脉冲频率 和FSH β基因，利用瞬时转染进行短期脉冲 治疗和稳定转染，用于在L β中进行更长时间的脉冲治疗 T2促性腺细胞系。 具体目标2：确定信号级联 确定诱导所需的信号转导途径， LH β与FSH β基因通过脉冲式GnRH。确定哪个信号 分子被特定的脉冲频率激活， 促性腺激素释放激素的激活。 具体目标3：确定转录机制 确定启动子区域和转录因子，发挥作用， LH β和FSH β基因的脉冲式GnRH诱导。确定新目标 使用DNA微阵列方法研究脉动GnRH基因。

DESCRIPTION (provided by applicant): The pulsatile secretion of gonadotropin-releasing hormone (GnRH) is the key regulator of reproduction. Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are differently regulated by different pulse frequencies of GnRH. The goal of this proposal is to determine the mechanism of regulation of LH and FSH gene expression by pulsatile GnRH. Specific Aim 1: Determine Pulse Frequencies Determine the GnRH pulse frequencies that lead to maximal expression of LH beta and FSHbeta genes utilizing transient transfection for short-term pulsatile treatment and stable transfection for longer pulsatile treatment in the L beta T2 gonadotrope cell line. Specific Aim 2: Determine Signaling Cascades Determine the signal transduction pathways necessary for the induction of LHbeta versus FSHbeta genes by pulsatile GnRH. Determine which signaling molecules are activated by specific pulse frequencies and compare their activation to tonic GnRH. Specific Aim 3: Determine the Transcriptional Mechanisms Determine the promoter regions and transcription factors that play roles in pulsatile GnRH induction of the LHbeta and FSHbeta genes. Identify new target genes for pulsatile GnRH using DNA microarray approaches.