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

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)4579-4587
Number of pages9
JournalEndocrinology
Volume157
Issue number12
DOIs
Publication statusPublished - 2016 Dec

Fingerprint

Lymphoid Tissue
Estradiol
Leukocytes
Aromatase
Peyer's Patches
Venules
Lymph Nodes
Gonads
Gonadal Steroid Hormones
Sex Characteristics
Estrogen Receptors
Transgenic Mice
Gastrointestinal Tract
Endothelial Cells
Immunohistochemistry

All Science Journal Classification (ASJC) codes

  • Endocrinology

Cite this

Oakley, O. R., Kim, K. J., Lin, P. C., Barakat, R., Cacioppo, J. A., Li, Z., ... Ko, C. M. (2016). Estradiol synthesis in gut-associated lymphoid tissue: Leukocyte regulation by a sexually monomorphic system. Endocrinology, 157(12), 4579-4587. https://doi.org/10.1210/en.2016-1391
Oakley, Oliver R. ; Kim, Kee Jun ; Lin, Po Ching ; Barakat, Radwa ; Cacioppo, Joseph A. ; Li, Zhong ; Whitaker, Alexandra ; Chung, Kwang Chul ; Mei, Wenyan ; Ko, Che Myong. / Estradiol synthesis in gut-associated lymphoid tissue : Leukocyte regulation by a sexually monomorphic system. In: Endocrinology. 2016 ; Vol. 157, No. 12. pp. 4579-4587.
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Oakley, OR, Kim, KJ, Lin, PC, Barakat, R, Cacioppo, JA, Li, Z, Whitaker, A, Chung, KC, Mei, W & Ko, CM 2016, 'Estradiol synthesis in gut-associated lymphoid tissue: Leukocyte regulation by a sexually monomorphic system', Endocrinology, vol. 157, no. 12, pp. 4579-4587. https://doi.org/10.1210/en.2016-1391

Estradiol synthesis in gut-associated lymphoid tissue : Leukocyte regulation by a sexually monomorphic system. / Oakley, Oliver R.; Kim, Kee Jun; Lin, Po Ching; Barakat, Radwa; Cacioppo, Joseph A.; Li, Zhong; Whitaker, Alexandra; Chung, Kwang Chul; Mei, Wenyan; Ko, Che Myong.

In: Endocrinology, Vol. 157, No. 12, 12.2016, p. 4579-4587.

Research output: Contribution to journalArticle

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T1 - Estradiol synthesis in gut-associated lymphoid tissue

T2 - Leukocyte regulation by a sexually monomorphic system

AU - Oakley, Oliver R.

AU - Kim, Kee Jun

AU - Lin, Po Ching

AU - Barakat, Radwa

AU - Cacioppo, Joseph A.

AU - Li, Zhong

AU - Whitaker, Alexandra

AU - Chung, Kwang Chul

AU - Mei, Wenyan

AU - Ko, Che Myong

PY - 2016/12

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N2 - 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.

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