title: Effects of testosterone and 17-beta-estradiol on TNF-alpha-induced E-selectin and VCAM-1 expression in endothelial cells. Analysis of the underlying receptor pathways.
abstract: This study investigated the effects of testosterone and 17-beta-estradiol on tumor necrosis factor-alpha (TNF-alpha)-induced endothelial expression of E-selectin and vascular cell adhesion molecule-1 (VCAM-1) and the potential roles of hormone receptors involved in these actions. Human umbilical vein endothelial cells (HUVEC) were stimulated with TNF-alpha in the presence or absence of testosterone or 17-beta-estradiol, and the expression of E-selectin and VCAM-1 was investigated. As shown by Western blot analysis, co-administration with testosterone or 17-beta-estradiol increased the expression of E-selectin and VCAM-1 induced by TNF-alpha at 6 h and 3 h, respectively. Similarly, RT-PCR analysis revealed a significant increase in the amount of mRNA for E-selectin and VCAM-1 after co-administration with testosterone or 17-beta-estradiol in TNF-alpha-stimulated HUVEC. The presence of mRNA and proteins for androgen receptor and estrogen receptor alpha in HUVEC was verified by RT-PCR and Western blot. Flow cytometric analysis showed that preincubation with androgen receptor antagonist cyproterone and estrogen receptor antagonist tamoxifen completely abrogated the upregulating effects of testosterone and 17-beta-estradiol on TNF-alpha-induced E-selectin and VCAM-1 expression, respectively. Expression of TNF receptors in TNF-alpha-stimulated HUVEC was not influenced by testosterone and 17-beta-estradiol. The data indicate that both testosterone and 17-beta-estradiol increase TNF-alpha-induced E-selectin and VCAM-1 expression in endothelial cells via a receptor-mediated system, and expression of TNF receptors are not changed in these actions. The implications of these results for the facilitory effects of both sex hormones on immune reactions are discussed.
authors.affiliation: Laboratory of Molecular Biology, Shanxi Medical University, 030001 Taiyuan, Shanxi, PR China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhang
authors.forename: Lian-Yun
authors.initials: LY
authors.lastname: Wang
authors.forename: Tian-Yun
authors.initials: TY
authors.lastname: Jiang
authors.forename: Hua-Ping
authors.initials: HP
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Dou
authors.forename: Jia-Hui
authors.initials: JH
authors.lastname: Zhao
authors.forename: Hong
authors.initials: H
authors.lastname: Zhao
authors.forename: Zhong-Dong
authors.initials: ZD
authors.lastname: Qiao
authors.forename: Jian-Tian
authors.initials: JT
authors.lastname: Qiao
mesh_terms: D059002:Androgen Receptor Antagonists; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics; D015153:Blotting, Western; D002460:Cell Line; D003864:Depression, Chemical; D019040:E-Selectin / Q000096:biosynthesis*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D011944:Receptors, Androgen / Q000187:drug effects; D011959:Receptors, Estradiol / Q000037:antagonists & inhibitors / Q000187:drug effects; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis / Q000235:genetics; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013739:Testosterone / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis*
chemical_list: D059002:Androgen Receptor Antagonists; D015703:Antigens, CD; D019040:E-Selectin; D011506:Proteins; D012333:RNA, Messenger; D011944:Receptors, Androgen; D011959:Receptors, Estradiol; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D013739:Testosterone; D004958:Estradiol