Estradiol synthesis in gut-associated lymphoid tissue: Leukocyte regulation by a sexually monomorphic system

Oliver R. Oakley, Kee Jun Kim, Po Ching Lin, Radwa Barakat, Joseph A. Cacioppo, Zhong Li, Alexandra Whitaker, Kwang Chul Chung, Wenyan Mei, Che Myong Ko

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8 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)4579-4587
Number of pages9
Issue number12
Publication statusPublished - 2016 Dec

Bibliographical note

Publisher Copyright:
Copyright © 2016 by the Endocrine Society.

All Science Journal Classification (ASJC) codes

  • Endocrinology


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