标题:Estradiol differentially regulates lipocalin-type prostaglandin D synthase transcript levels in the rodent brain: Evidence from high-density oligonucleotide arrays and in situ hybridization
期刊名称:Proceedings of the National Academy of Sciences
印刷版ISSN:0027-8424
电子版ISSN:1091-6490
出版年度:2003
卷号:100
期号:1
页码:318-323
DOI:10.1073/pnas.262663799
语种:English
出版社:The National Academy of Sciences of the United States of America
摘要:Microarrays comprise an efficient approach to discovering large numbers of differentially expressed mRNA transcripts in the CNS resulting from changes in hormonal milieu. We used high-density oligonucleotide microarrays to examine the short- and long-term actions of estradiol (E2) on the transcriptomes from the medial basal hypothalamus and other brain regions of E2-treated (10 {micro}g) adult female mice. Our results have revealed several unanticipated gene regulations. Most striking is lipocalin prostaglandin D2 synthase (L-PGDS), which catalyzes the conversion of prostaglandin (PG) H2 to PGD2, a neuromodulator involved in a variety of functions, including sleep, pain, and odor responses. In situ hybridization revealed significant increases in L-PGDS expression in the arcuate and ventromedial nucleus of the medial basal hypothalamus compared with vehicle controls. The magnitude of these changes is {approx}2-fold and suggests a modulatory role for PGD2 in E2-controlled neuroendocrine secretions and behaviors. Surprisingly, L-PGDS gene expression is reduced 2-fold after E2 treatment in the ventrolateral preoptic area (VLPO), the suspected site of action for the sleep-promoting effects of PGD2. Finally, whereas L-PGDS has been reported to be expressed primarily in oligodendrocytes of the adult rodent brain, we demonstrate, immunocytochemically, that L-PGDS is also expressed in a population of VLPO neurons. Thus, our data suggest the intriguing possibility that E2 modulation of L-PGDS plays a role in the regulation of sleep-wake states through hitherto unknown mechanisms in VLPO neurons and through hormone-dependent neuronal-glial cooperation.