title: Estradiol differentially regulates lipocalin-type prostaglandin D synthase transcript levels in the rodent brain: Evidence from high-density oligonucleotide arrays and in situ hybridization.
abstract: 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 (E(2)) on the transcriptomes from the medial basal hypothalamus and other brain regions of E(2)-treated (10 microg) adult female mice. Our results have revealed several unanticipated gene regulations. Most striking is lipocalin prostaglandin D(2) synthase (L-PGDS), which catalyzes the conversion of prostaglandin (PG) H(2) to PGD(2), 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 approximately 2-fold and suggests a modulatory role for PGD(2) in E(2)-controlled neuroendocrine secretions and behaviors. Surprisingly, L-PGDS gene expression is reduced 2-fold after E(2) treatment in the ventrolateral preoptic area (VLPO), the suspected site of action for the sleep-promoting effects of PGD(2). 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 E(2) 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.
authors.affiliation: Laboratory of Neurobiology and Behavior, The Rockefeller University, 1230 York Ave, New York, NY 10021, USA. mongj@rockefeller.edu
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Mong
authors.forename: Nino
authors.initials: N
authors.lastname: Devidze
authors.forename: Donald E
authors.initials: DE
authors.lastname: Frail
authors.forename: Lawrence T
authors.initials: LT
authors.lastname: O'Connor
authors.forename: Manjo
authors.initials: M
authors.lastname: Samuel
authors.forename: Elena
authors.initials: E
authors.lastname: Choleris
authors.forename: Sonoko
authors.initials: S
authors.lastname: Ogawa
authors.forename: Donald W
authors.initials: DW
authors.lastname: Pfaff
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D001921:Brain / Q000201:enzymology*; D017931:DNA Primers; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D019746:Intramolecular Oxidoreductases / Q000235:genetics*; D054834:Lipocalins; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D012016:Reference Values; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: D017931:DNA Primers; D054834:Lipocalins; D004958:Estradiol; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase