HORMONE CONTROL OF B-LUTEINIZING HORMONE GENE EXPRESSION

点击翻译按钮获取中文摘要

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.