title: Estradiol Synthesis in Gut-Associated Lymphoid Tissue: Leukocyte Regulation by a Sexually Monomorphic System.
abstract: 17β-estradiol is a potent sex hormone synthesized primarily by gonads in females and males that regulates development and function of the reproductive system. Recent studies show that 17β-estradiol is locally synthesized in nonreproductive tissues and regulates a myriad of events, including local inflammatory responses. In this study, we report that mesenteric lymph nodes (mLNs) and Peyer's patches (Pps) are novel sites of de novo synthesis of 17β-estradiol. These secondary lymphoid organs are located within or close to the gastrointestinal tract, contain leukocytes, and function at the forefront of immune surveillance. 17β-estradiol synthesis was initially identified using a transgenic mouse with red fluorescent protein coexpressed in cells that express aromatase, the enzyme responsible for 17β-estradiol synthesis. Subsequent immunohistochemistry and tissue culture experiments revealed that aromatase expression was localized to high endothelial venules of these lymphoid organs, and these high endothelial venule cells synthesized 17β-estradiol when isolated and cultured in vitro. Both mLNs and Pps contained 17β-estradiol with concentrations that were significantly higher than those of peripheral blood. Furthermore, the total amount of 17β-estradiol in these organs exceeded that of the gonads. Mice lacking either aromatase or estrogen receptor-β had hypertrophic Pps and mLNs with more leukocytes than their wild-type littermates, demonstrating a role for 17β-estradiol in leukocyte regulation. Importantly, we did not observe any sex-dependent differences in aromatase expression, 17β-estradiol content, or steroidogenic capacity in these lymphoid organs.
authors: Department of Biology (O.R.O., A.W.), Eastern Kentucky University, Richmond, Kentucky 40475; Roy J. Carver Biotechnology Center (K.J.K., Z.L.), University of Illinois at Urbana-Champaign, Urbana, Illinois 61801; Department of Comparative Biosciences (P.-C.L., R.B., J.A.C., W.M., C.K.), University of Illinois at Urbana-Champaign, Urbana, Illinois 61802; Faculty of Veterinary Medicine (R.B.), Benha University, Benha 13518, Egypt; and Department of Systems Biology (C.C.), Yonsei University, Seodaemun-gu, Seoul 120-749, Republic of Korea.
authors: Oliver R
authors: OR
authors: Oakley
authors: Department of Biology (O.R.O., A.W.), Eastern Kentucky University, Richmond, Kentucky 40475; Roy J. Carver Biotechnology Center (K.J.K., Z.L.), University of Illinois at Urbana-Champaign, Urbana, Illinois 61801; Department of Comparative Biosciences (P.-C.L., R.B., J.A.C., W.M., C.K.), University of Illinois at Urbana-Champaign, Urbana, Illinois 61802; Faculty of Veterinary Medicine (R.B.), Benha University, Benha 13518, Egypt; and Department of Systems Biology (C.C.), Yonsei University, Seodaemun-gu, Seoul 120-749, Republic of Korea.
authors: Kee Jun
authors: KJ
authors: Kim
authors: Department of Biology (O.R.O., A.W.), Eastern Kentucky University, Richmond, Kentucky 40475; Roy J. Carver Biotechnology Center (K.J.K., Z.L.), University of Illinois at Urbana-Champaign, Urbana, Illinois 61801; Department of Comparative Biosciences (P.-C.L., R.B., J.A.C., W.M., C.K.), University of Illinois at Urbana-Champaign, Urbana, Illinois 61802; Faculty of Veterinary Medicine (R.B.), Benha University, Benha 13518, Egypt; and Department of Systems Biology (C.C.), Yonsei University, Seodaemun-gu, Seoul 120-749, Republic of Korea.
authors: Po-Ching
authors: PC
authors: Lin
authors: Department of Biology (O.R.O., A.W.), Eastern Kentucky University, Richmond, Kentucky 40475; Roy J. Carver Biotechnology Center (K.J.K., Z.L.), University of Illinois at Urbana-Champaign, Urbana, Illinois 61801; Department of Comparative Biosciences (P.-C.L., R.B., J.A.C., W.M., C.K.), University of Illinois at Urbana-Champaign, Urbana, Illinois 61802; Faculty of Veterinary Medicine (R.B.), Benha University, Benha 13518, Egypt; and Department of Systems Biology (C.C.), Yonsei University, Seodaemun-gu, Seoul 120-749, Republic of Korea.
authors: Radwa
authors: R
authors: Barakat
authors: Department of Biology (O.R.O., A.W.), Eastern Kentucky University, Richmond, Kentucky 40475; Roy J. Carver Biotechnology Center (K.J.K., Z.L.), University of Illinois at Urbana-Champaign, Urbana, Illinois 61801; Department of Comparative Biosciences (P.-C.L., R.B., J.A.C., W.M., C.K.), University of Illinois at Urbana-Champaign, Urbana, Illinois 61802; Faculty of Veterinary Medicine (R.B.), Benha University, Benha 13518, Egypt; and Department of Systems Biology (C.C.), Yonsei University, Seodaemun-gu, Seoul 120-749, Republic of Korea.
authors: Joseph A
authors: JA
authors: Cacioppo
authors: Department of Biology (O.R.O., A.W.), Eastern Kentucky University, Richmond, Kentucky 40475; Roy J. Carver Biotechnology Center (K.J.K., Z.L.), University of Illinois at Urbana-Champaign, Urbana, Illinois 61801; Department of Comparative Biosciences (P.-C.L., R.B., J.A.C., W.M., C.K.), University of Illinois at Urbana-Champaign, Urbana, Illinois 61802; Faculty of Veterinary Medicine (R.B.), Benha University, Benha 13518, Egypt; and Department of Systems Biology (C.C.), Yonsei University, Seodaemun-gu, Seoul 120-749, Republic of Korea.
authors: Zhong
authors: Z
authors: Li
authors: Department of Biology (O.R.O., A.W.), Eastern Kentucky University, Richmond, Kentucky 40475; Roy J. Carver Biotechnology Center (K.J.K., Z.L.), University of Illinois at Urbana-Champaign, Urbana, Illinois 61801; Department of Comparative Biosciences (P.-C.L., R.B., J.A.C., W.M., C.K.), University of Illinois at Urbana-Champaign, Urbana, Illinois 61802; Faculty of Veterinary Medicine (R.B.), Benha University, Benha 13518, Egypt; and Department of Systems Biology (C.C.), Yonsei University, Seodaemun-gu, Seoul 120-749, Republic of Korea.
authors: Alexandra
authors: A
authors: Whitaker
authors: Department of Biology (O.R.O., A.W.), Eastern Kentucky University, Richmond, Kentucky 40475; Roy J. Carver Biotechnology Center (K.J.K., Z.L.), University of Illinois at Urbana-Champaign, Urbana, Illinois 61801; Department of Comparative Biosciences (P.-C.L., R.B., J.A.C., W.M., C.K.), University of Illinois at Urbana-Champaign, Urbana, Illinois 61802; Faculty of Veterinary Medicine (R.B.), Benha University, Benha 13518, Egypt; and Department of Systems Biology (C.C.), Yonsei University, Seodaemun-gu, Seoul 120-749, Republic of Korea.
authors: Kwang Chul
authors: KC
authors: Chung
authors: Department of Biology (O.R.O., A.W.), Eastern Kentucky University, Richmond, Kentucky 40475; Roy J. Carver Biotechnology Center (K.J.K., Z.L.), University of Illinois at Urbana-Champaign, Urbana, Illinois 61801; Department of Comparative Biosciences (P.-C.L., R.B., J.A.C., W.M., C.K.), University of Illinois at Urbana-Champaign, Urbana, Illinois 61802; Faculty of Veterinary Medicine (R.B.), Benha University, Benha 13518, Egypt; and Department of Systems Biology (C.C.), Yonsei University, Seodaemun-gu, Seoul 120-749, Republic of Korea.
authors: Wenyan
authors: W
authors: Mei
authors: Department of Biology (O.R.O., A.W.), Eastern Kentucky University, Richmond, Kentucky 40475; Roy J. Carver Biotechnology Center (K.J.K., Z.L.), University of Illinois at Urbana-Champaign, Urbana, Illinois 61801; Department of Comparative Biosciences (P.-C.L., R.B., J.A.C., W.M., C.K.), University of Illinois at Urbana-Champaign, Urbana, Illinois 61802; Faculty of Veterinary Medicine (R.B.), Benha University, Benha 13518, Egypt; and Department of Systems Biology (C.C.), Yonsei University, Seodaemun-gu, Seoul 120-749, Republic of Korea.
authors: CheMyong
authors: C
authors: Ko
mesh_terms: D000818:Animals; D001141:Aromatase / Q000235:genetics / Q000378:metabolism*; D004958:Estradiol / Q000096:biosynthesis*; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism; D005260:Female; D006066:Gonads / Q000378:metabolism; D007150:Immunohistochemistry; D007962:Leukocytes / Q000378:metabolism*; D008198:Lymph Nodes / Q000378:metabolism*; D008297:Male; D008643:Mesentery / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010581:Peyer's Patches / Q000378:metabolism*; D013154:Spleen / Q000378:metabolism
chemical_list: D047629:Estrogen Receptor beta; D004958:Estradiol; D001141:Aromatase