Evidence for the genetic control of estradiol-regulated responses. Implications for variation in normal and pathological hormone-dependent phenotypes

Am J Pathol. 1997 Jun;150(6):2223-30.


The ovarian steroid hormone estrogen (E2) elicits a multiplicity of both systemic and uterotropic responses in vivo. For example, the administration of E2 to ovariectomized (Ovx) and sexually immature rodents leads to uterine-specific inflammatory infiltrates. In this study, we quantitated the number of eosinophils and BM8+, Ia+, and CD4+ cells in uteri obtained from adult Ovx control and E2-treated C57BL/6J, C3H/HeJ, and (C57BL/6J x C3H/HeJ) (B6C3) F1 hybrid mice. All three strains exhibited a significant increase in the number of uterine eosinophils and BM8+ macrophages after E2 treatment. However, C57BL/6J and B6C3 F1 hybrid mice responded with a greater number of infiltrating eosinophils and macrophages as compared with C3H/HeJ. A similar analysis of Ia+ and CD4+ cells showed that E2 treatment either down-regulates or does not affect the number of such cells in all three strains. Genome exclusion mapping using a (C57BL/6J x C3H/HeJ) x C3H/HeJ backcross population localized Est1, the major locus controlling the number of eosinophils infiltrating the uterus after E2 treatment, to chromosome 4. In addition, suggestive linkage to marker loci on chromosomes 10 and 16 was detected and evidence for locus interaction is presented. Our results conclusively demonstrate that E2-regulated/ dependent responses can be genetically controlled, indicating that the phenotypic variation observed in both the normal and pathological effects of E2 may, in part, be due to a genetic component.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / drug effects
  • Chromosome Mapping*
  • Eosinophils / drug effects
  • Eosinophils / immunology*
  • Estradiol / pharmacology*
  • Female
  • Genetic Linkage
  • Inflammation / genetics*
  • Inflammation / immunology
  • Macrophages / drug effects
  • Macrophages / immunology
  • Mice
  • Mice, Inbred Strains
  • Ovariectomy
  • Species Specificity
  • Uterus / immunology*


  • Estradiol