VITAMIN A IN GROWTH AND DEVELOPMENT

拟议的营养和生物化学研究的目的是 继续确定微量营养素作用的分子机制 维生素A（视黄醇）及其代谢产物视黄酸在发育器官中的作用 除了眼睛。视黄醇和视黄酸与基因组的相互作用 将在肺、肝和睾丸的围产期发育期间进行研究。 在视黄醇缺乏时基因表达发生的变化， 在整个动物中进行研究，通过饮食使视黄醇缺乏 限制和补充视黄醇或视黄酸后不久 （再喂养模型）。在分析这种营养素与 基因组，两个特定的细胞内结合蛋白的视黄醇（CRABP）和 视黄酸（CRABP）将受到特别关注。使用 再喂养模型，它将探讨是否以及如何基因编码的 这些蛋白质由它们各自的配体和激素调节。 此外，还将研究这些蛋白质的基因是如何被 在围产期发育过程中调节各种器官， 强调肺和睾丸的分化。细胞表达 这些结合蛋白的基因将在肺和 睾丸组织将试图阐明组织特异性 通过研究蛋白质结合的视黄醇和视黄酸的作用， CRBP和CRABP基因的启动子区。最后提出了实验方案 检测和表征由视黄醇和维甲酸激活的早期基因， 酸

The objective of the proposed nutritional and biochemical research is to continue to define molecular mechanism(s) of action of micronutrient vitamin A (retinol) and its metabolite retinoic acid in developing organs other than the eye. Retinol and retinoic acid interactions with the genome will be studied during perinatal development of lungs, liver, and testes. Changes which occur in the gene expression during retinol deficiency will be studied in the whole animal made retinol deficient by dietary restriction and shortly after refeeding with retinol or retinoic acid (refeeding model). In the analysis of interaction of this nutrient with the genome, two specific intracellular binding proteins for retinol (CRABP) and for retinoic acid (CRABP) will receive particular attention. Using the refeeding model, it will be explored whether and how the genes coding for these proteins are regulated by their respective ligands and by hormones. Furthermore, it will be studied how genes for these proteins are being regulated during perinatal development of various organs with special emphasis on the lung and testicular differentiation. The cells expressing genes for these binding proteins will be identified in pulmonary and testicular tissue. It will be attempted to clarify the tissue specific action of retinol and retinoic acid by studying proteins binding to the promoter regions of CRBP and CRABP genes. Finally, experiments are proposed to detect and characterize early genes activated by retinol and retinoic acid.