Estradiol regulates MICA expression in human endometrial cells

Clin Immunol. 2008 Nov;129(2):325-32. doi: 10.1016/j.clim.2008.07.005. Epub 2008 Aug 26.


The human endometrium undergoes cyclical changes regulated by sex hormones. Evidence suggests that sex hormones regulate NK cell recruitment into the uterus in large numbers. NKG2D is an activating receptor expressed on human NK cells, gammadelta and CD8 T cells. NKG2D ligands are known to be sensors of cellular "stress". In this study, we investigated whether sex hormones directly regulate expression of NKG2D ligands in the human uterus. Estradiol increased MICA expression on uterine epithelial cells; regulation was estrogen receptor-dependent. Real-time PCR analysis showed that NKG2D ligands MICA and MICB were expressed in the human endometrium. MICA protein was detected primarily on epithelial cells, and greater expression was observed in immunohistochemical analysis of tissues from patients in the secretory phase of the menstrual cycle. Thus, estrogens regulate expression of MICA. These data suggest hormonal regulation of innate immunity and NKG2D-mediated recognition in other tissues and diseases where estrogen may be involved.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cell Line, Tumor
  • Endometrium / immunology*
  • Estradiol / pharmacology*
  • Female
  • GPI-Linked Proteins
  • Gene Expression Regulation / drug effects*
  • Histocompatibility Antigens Class I / analysis
  • Histocompatibility Antigens Class I / genetics*
  • Histocompatibility Antigens Class I / physiology
  • Humans
  • Intercellular Signaling Peptides and Proteins / analysis
  • RNA, Messenger / analysis


  • GPI-Linked Proteins
  • Histocompatibility Antigens Class I
  • Intercellular Signaling Peptides and Proteins
  • MHC class I-related chain A
  • RNA, Messenger
  • ULBP2 protein, human
  • Estradiol