First Author | Oakley OR | Year | 2016 |
Journal | Endocrinology | Volume | 157 |
Issue | 12 | Pages | 4579-4587 |
PubMed ID | 27779914 | Mgi Jnum | J:240812 |
Mgi Id | MGI:5896467 | Doi | 10.1210/en.2016-1391 |
Citation | Oakley OR, et al. (2016) Estradiol Synthesis in Gut-Associated Lymphoid Tissue: Leukocyte Regulation by a Sexually Monomorphic System. Endocrinology 157(12):4579-4587 |
abstractText | 17beta-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 17beta-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 17beta-estradiol. These secondary lymphoid organs are located within or close to the gastrointestinal tract, contain leukocytes, and function at the forefront of immune surveillance. 17beta-estradiol synthesis was initially identified using a transgenic mouse with red fluorescent protein coexpressed in cells that express aromatase, the enzyme responsible for 17beta-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 17beta-estradiol when isolated and cultured in vitro. Both mLNs and Pps contained 17beta-estradiol with concentrations that were significantly higher than those of peripheral blood. Furthermore, the total amount of 17beta-estradiol in these organs exceeded that of the gonads. Mice lacking either aromatase or estrogen receptor-beta had hypertrophic Pps and mLNs with more leukocytes than their wild-type littermates, demonstrating a role for 17beta-estradiol in leukocyte regulation. Importantly, we did not observe any sex-dependent differences in aromatase expression, 17beta-estradiol content, or steroidogenic capacity in these lymphoid organs. |