title: Studies on estrogen receptor (ER) alpha and beta responses on gene regulation in peripheral blood leukocytes in vivo using selective ER agonists.
abstract: Major reproductive events such as menstruation, ovulation, implantation, and cervical ripening are characterized by an increased number of invading leukocytes in the tissues. Sex steroid hormones, particularly estrogens, play an important role in these dynamic changes in the female reproductive tract. Estrogens have also been implicated in the pathogenesis of many common pathological conditions associated with leukocyte infiltration and immunological dysfunction, such as auto-immune diseases and atherosclerosis. Although the two estrogen receptor (ER) subtypes, ERalpha and ERbeta, have been found in different leukocyte populations in tissues and in peripheral blood, there is still very little known about functional activity and importance of ERs in blood cells. To elucidate the different roles for ERalpha and ERbeta in peripheral blood leukocytes, we used microarray gene expression profiling of rat peripheral blood leukocytes subjected to in vivo treatment with estradiol (E2), the selective ERalpha agonist 4,4',4''-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT), and the selective ERbeta agonist 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN). We report the identification of genes that were commonly regulated by E2, PPT, and DPN, and genes that were regulated either by the ERalpha or ERbeta agonist. Further confirmatory analyses of the selected regulated genes 12-lipoxygenase, fibulin-1, furin, and calgranulin B are also presented. These results were then compared with those from the uterine tissue of the same animals. Our study demonstrates that peripheral blood leukocytes are responsive to estrogens. E2 and selective ERalpha and ERbeta agonists regulate a number of genes that may contribute to inflammation and remodeling of the extracellular matrix.
authors.affiliation: Division for Reproductive Endocrinology, Department of Woman and Child Health, Karolinska Institutet, Karolinska University Hospital Solna, Q2:08, S-171 76 Stockholm, Sweden.
authors.forename: Denis
authors.initials: D
authors.lastname: Stygar
authors.forename: Britt
authors.initials: B
authors.lastname: Masironi
authors.forename: Håkan
authors.initials: H
authors.lastname: Eriksson
authors.forename: Lena
authors.initials: L
authors.lastname: Sahlin
mesh_terms: D000818:Animals; D001092:Arachidonate 12-Lipoxygenase / Q000235:genetics; D001483:Base Sequence; D002135:Calcium-Binding Proteins / Q000235:genetics; D040502:Calgranulin B / Q000235:genetics; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000378:metabolism*; D005260:Female; D045683:Furin / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D007962:Leukocytes / Q000378:metabolism*; D008969:Molecular Sequence Data; D009243:NAD / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis; D010636:Phenols; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014599:Uterus / Q000378:metabolism
chemical_list: D002135:Calcium-Binding Proteins; D040502:Calgranulin B; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D010636:Phenols; D011720:Pyrazoles; C060820:fibulin; C486184:4,4',4''-(4-propyl-((1)H)-pyrazole-1,3,5-triyl) tris-phenol; D009243:NAD; D004958:Estradiol; D001092:Arachidonate 12-Lipoxygenase; D045683:Furin