Gene expression profiling in the human hypothalamus-pituitary-adrenal axisand full-length cDNA cloning

The primary neuroendocrine interface, hypothalamus and pituitary, together with adrenals, constitute the major axis responsible for the maintenance of homeostasis and the response to the perturbations in the environment. The gene expression profiling in the human hypothalamus-pituitary-adrenal axis was catalogued by generating a large amount of expressed sequence tags (EST s), followed by bioinformatics analysis (http://www.chgc.sh.cn/database). T otally, 25,973 sequences of good quality were obtained from 31,130 clones ( 83.4%) from cDNA libraries of the hypothalamus, pituitary, and adrenal glan ds. After eliminating 5,347 sequences corresponding to repetitive elements and mtDNA, 20,626 ESTs could be assembled into 9,175 clusters (3,979, 3,074 , and 4,116 clusters in hypothalamus, pituitary, and adrenal glands, respec tively) when overlapping ESTs were integrated. Of these clusters, 2,777 (30 .3%) corresponded to known genes, 4,165 (44.8%) to dbESTs, and 2,233 (24.3% ) to novel ESTs. The gene expression profiles reflected well the functional characteristics of the th ree levels in the hypothalamus-pituitary-adrenal axis, because most of the 20 genes with highest expression showed statisti cal difference in terms of tissue distribution, including a group of tissue -specific functional markers. Meanwhile, some findings were made with regar d to the physiology of the axis, and 200 full-length cDNAs of novel genes w ere cloned and sequenced. All of these data may contribute to the understan ding of the neuroendocrine regulation of human life.