Regulation of Gonadotropin Expression by GnRH Pulses

描述(申请人提供)：脉冲性分泌物 促性腺激素释放激素(GnRH)是生殖的关键调节因子。 卵泡刺激素(FSH)和黄体生成素(LH)是不同的 受不同脉冲频率的促性腺激素释放激素调节。这项提议的目标是 探讨黄体生成素对促黄体生成素和卵泡刺激素基因表达的调节机制 搏动性促性腺激素释放激素。 具体目标1：确定脉冲频率 确定导致促黄体生成素β最大表达的促性腺激素释放激素脉冲频率 和FSHβ基因的瞬时转染法进行短期搏动 Lβ细胞长脉冲治疗及稳定转染法的研究 T2促性腺激素细胞株。 具体目标2：确定信令级联 确定诱导细胞死亡所需的信号转导途径 脉冲性促性腺激素释放激素与促性腺激素释放激素β基因的比较。确定哪个信令 分子被特定的脉冲频率激活，并比较它们的 激活补充性促性腺激素释放激素。 具体目标3：确定转录机制 确定起作用的启动子区域和转录因子 脉冲性促性腺激素释放激素对LHbeta和FSHbeta基因的诱导确定新目标 用DNA微阵列方法研究脉动性促性腺激素释放激素基因。

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.