Normal development of thymus in male and female mice requires estrogen/estrogen receptor-α signaling pathway

Srikanth Yellayi, Cory Teuscher, Jeffery A. Woods, Thomas H. Welsh, Kenneth S K Tung, Masaaki Nakai, Cheryl S. Rosenfeld, Dennis B. Lubahn, Paul S. Cooke

Research output: Contribution to journalArticlepeer-review


Estrogen receptors (ERs) are expressed in the thymus of both males and females, but their role in thymic development and function is unclear. To determine whether ERα plays a role in thymic function of either males or females, we compared thymuses of male and female wild-type (WT) and ERα knockout (αERKO) mice from birth to adulthood. Although thymic size was similar in both male and female WT and αERKO mice at birth (d 0), by postnatal d 5 and at all subsequent ages, both male and female αERKO mice had significant (30-55%) reductions in thymic weight. Morphometric analysis revealed a reduction in thymic medullary areas in adult αERKO mice compared with age-matched WT controls that paralleled thymic involution. There were changes in relative percentages of CD4+ and CD4+CD8+ T-cells, and large decreases (70-80%) in overall absolute numbers of CD4+ and CD4+CD8+ T- cells. Serum corticosterone and testosterone levels were not different in either neonatal or adult male WT or αERKO mice, and serum levels of 17β- estradiol (E2) were similar in neonatal WT and αERKO males, indicating that increases in these thymolytic hormones are not responsible for the decreased thymic weight in αERKO males. Additionally, delayed-type hypersensitivity was significantly increased in male αERKO mice compared with WT mice. In summary, ERα deficiency does not inhibit initial differentiation or fetal thymic development, but the absence of ERα results in marked decreases in thymic size in both sexes during the postnatal period. These results are the first direct demonstration that the E2/ERα signaling system is necessary for maintenance of normal postnatal function of the female thymus gland. The similar results obtained in males demonstrate a role for the E2/ERα signaling system in the male thymus and emphasize that estrogens play a more critical role in the male than previously realized.

Original languageEnglish (US)
Pages (from-to)207-213
Number of pages7
Issue number3
StatePublished - 2000


  • Immune
  • Sex steroids
  • Thymic growth
  • Thymolysis
  • α ERKO mouse

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology


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