title: Global transcription profiling of estrogen activity: estrogen receptor alpha regulates gene expression in the kidney.
abstract: Estrogen receptors (ERs) are expressed in numerous organs, although only a few organs are considered classical targets for estrogens. We have completed a systematic survey of estrogen regulation of approximately 10,000 genes in 13 tissues from wild-type and ERbetaKO mice treated sc with vehicle or 17beta-estradiol (E2) for 6 wk. The uterus and pituitary had the greatest number of genes regulated by E2, whereas the kidney had the third largest number of regulated genes. In situ hybridizations localized E2 regulation in the kidney to the juxtamedullary region of the cortex in both the mouse and rat. The ED(50) for gene inductions in the kidney was 3 micro g/kg.d, comparable with the 2.4 micro g/kg.d ED(50) for c-fos induction in the uterus. E2 regulations in the kidney were intact in ERbetaKO mice, and the ERalpha-selective agonist propylpyrazole triol acted similarly to E2, together suggesting an ERalpha-mediated mechanism. Several genes were induced within 2 h of E2 treatment, suggesting a direct activity of ERalpha within the kidney. Finally, the combination of the activation function (AF)1-selective agonist tamoxifen plus ERalphaKO(CH) mice expressing an AF1-deleted version of ERalpha allowed delineation of genes with differing requirements for AF1 or AF2 activity in the kidney.
authors.affiliation: Genomics Department, Wyeth Research, Cambridge, Massachusetts 02140, USA.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Jelinsky
authors.forename: Heather A
authors.initials: HA
authors.lastname: Harris
authors.forename: Eugene L
authors.initials: EL
authors.lastname: Brown
authors.forename: Kathryn
authors.initials: K
authors.lastname: Flanagan
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Zhang
authors.forename: Christopher
authors.initials: C
authors.lastname: Tunkey
authors.forename: KehDih
authors.initials: K
authors.lastname: Lai
authors.forename: Malcolm V
authors.initials: MV
authors.lastname: Lane
authors.forename: Donna K
authors.initials: DK
authors.lastname: Simcoe
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Evans
mesh_terms: D000818:Animals; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects* / Q000502:physiology; D007668:Kidney / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D010902:Pituitary Gland / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology*; D014599:Uterus / Q000502:physiology
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D011960:Receptors, Estrogen