GPR30 contributes to estrogen-induced thymic atrophy

Chunhe Wang, Babak Dehghani, I. Jack Magrisso, Elizabeth A. Rick, Edna Bonhomme, David B. Cody, Laura A. Elenich, Sandhya Subramanian, Stephanie J. Murphy, Martin J. Kelly, Jan S. Rosenbaum, Arthur A. Vandenbark, Halina Offner

Research output: Contribution to journalArticle

158 Scopus citations

Abstract

The mechanisms by which prolonged estrogen exposures, such as estrogen therapy and pregnancy, reduce thymus weight, cellularity, and CD4 and CD8 phenotype expression, have not been well defined. In this study, the roles played by the membrane estrogen receptor, G protein-coupled receptor 30 (GPR30), and the intracellular estrogen receptors, estrogen receptor α (ERα) and β (ERβ), in 17β-estradiol (E2)-induced thymic atrophy were distinguished by construction and the side-by-side comparison of GPR30-deficient mice with ERα and ERβ gene-deficient mice. Our study shows that whereas ERα mediated exclusively the early developmental blockage of thymocytes, GPR30 was indispensable for thymocyte apoptosis that preferentially occurs in T cell receptor β chain-/low double-positive thymocytes. Additionally, G1, a specific GPR30 agonist, induces thymic atrophy and thymocyte apoptosis, but not developmental blockage. Finally, E2 treatment attenuates the activation of nuclear factor-κB in CD25-CD4 -CD8- double-negative thymocytes through an ERα-dependent yet ERα- and GPR30-independent pathway. Differential inhibition of nuclear factor-κB by ERα and GPR30 might underlie their disparate physiological effects on thymocytes. Our study distinguishes, for the first time, the respective contributions of nuclear and membrane E2 receptors in negative regulation of thymic development.

Original languageEnglish (US)
Pages (from-to)636-648
Number of pages13
JournalMolecular Endocrinology
Volume22
Issue number3
DOIs
StatePublished - Mar 2008

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

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    Wang, C., Dehghani, B., Magrisso, I. J., Rick, E. A., Bonhomme, E., Cody, D. B., Elenich, L. A., Subramanian, S., Murphy, S. J., Kelly, M. J., Rosenbaum, J. S., Vandenbark, A. A., & Offner, H. (2008). GPR30 contributes to estrogen-induced thymic atrophy. Molecular Endocrinology, 22(3), 636-648. https://doi.org/10.1210/me.2007-0359