HORMONE CONTROL OF B-LUTEINIZING HORMONE GENE EXPRESSION

促性腺激素基因表达的内分泌调节是促性腺激素分泌的核心。 控制繁殖。 促性腺激素的激素调节 分泌是很好的特点，内分泌的分子性质 促性腺激素基因表达的调节还不清楚。 的 该提案的目的是确定规范 表达大鼠基因编码β促黄体生成激素（LH）， 赋予该分子生物特异性的亚基。 具体地说， 利用分离的、充分表征的β LH的重组DNA方法 互补DNA（cDNA）和基因组克隆将用于探测 内分泌诱导的β LH信使RNA（mRNA）浓度的变化， 垂体前叶细胞 此外，这些探针将允许生物化学 解剖控制β LH基因转录的内分泌事件， β LH mRNA降解，这两个过程决定了整体细胞 mRNA丰度。 β LH基因表达的调节将在原发性前额叶皮层中进行检查。 垂体细胞培养到下丘脑/垂体复合体 存在于体内的相互作用，并允许直接检查激素 体外β LH mRNA丰度的调节。 特别是这些 研究将确定激素是否可以通过以下方式控制LH分泌： 它们对β LH表达的调节。 性腺激素释放激素 促性腺激素释放激素（GnRH）和性腺类固醇各自有助于调节LH分泌： β LH mRNA的定量将确定是否有GnRH、雌二醇或 孕酮对β LH基因表达也有平行影响。 在 此外，类固醇与GnRH的相互作用改变了垂体LH分泌， 还将检查细胞β LH mRNA的伴随调节 丰饶。 最后，环核苷酸作为介质的假定作用 通过测定外源性环腺苷酸是否 或环GMP类似物改变培养的前房细胞中β LH基因表达 垂体细胞 这些研究将提供重要的基础知识， 控制β LH基因表达的机制，从而增强 目前对生育调控的认识。 此外，他们将提供 一个有用的研究基因的激素调节的通用范式 表情

Endocrine regulation of gonadotropin gene expression is central to the control of reproduction. While hormone modulation of gonadotropin secretion is well-characterized, the molecular nature of endocrine regulation of gonadotropin gene expression is not yet understood. The objective of this proposal is to define processes which regulate expressions of the rat gene encoding beta luteinizing hormone (LH), the subunit conferring biological specificity to this molecule. Specifically, recombinant DNA methods utilizing isolated, well-charaterized beta LH complemantary DNA (cDNA) and genomic clones will be used to probe endocrine-induced changes in beta LH messenger RNA (mRNA) concentration in anterior pituitary cells. Moreover, these probes will permit biochemical dissection of endocrine events which govern beta LH gene transcription and beta LH mRNA degradation, two processes which determine overall cellular mRNA abundance. Regulation of beta LH gene expression will be examined in primary anterior pituitary cell cultures to obviate complex hypothalamo/hypophyseal interactions present in vivo, and permit direct examination of the hormonal modulation of beta LH mRNA abundance in vitro. In particular, these studies will determine whether hormones can control LH secretion through their regulation of beta LH expression. Gonadotropin-releasing hormone (GnRH) and gonadal steroids each contribute to regulation of LH secretion: quantitation of beta LH mRNA will determine whether GnRH, estradiol or progesterone elicit parallel effects on beta LH gene expression. In addition, steroid interactions with GnRH which alter pituitary LH secretion will also be examined for concomitant modulation of cellular beta LH mRNA abundance. Finally, the postulated role of cyclic nucleotides as mediators of GnRH action will be examined by determining whether exogenous cyclic AMP or cyclic GMP analogs alter beta LH gene expression in cultured anterior pituicytes. These studies will provide important basic knowledge about molecular machanisms which control expression of the beta LH gene, thereby enhancing current understanding of fertility regulation. Moreover, they will provide a useful generalized paradigm to study hormonal regulation of gene expression.