Estrogen receptor alpha is necessary in thymic development and estradiol-induced thymic alterations

Estrogens affect the development, maturation, and function of multiple orga n systems, including the immune system, One of the main targets of estrogen s in the immune system is the thymus, which undergoes atrophy and phenotypi c alterations when exposed to elevated levels of estrogen, To determine how estrogens influence the thymus and affect T cell development, estrogen rec eptor alpha (ER alpha) knockout (ERKO) mice were examined. ERKO mice have s ignificantly smaller thymi than their wild-type (WT) littermates. Construct ion of ER radiation bone marrow chimeras indicated that the smaller thymi w ere due to a lack of ERa in radiation-resistant tissues rather than hemopoi etic elements. ERKO mice were also susceptible to estradiol-induced thymic atrophy, but the extent of their atrophy was less than what was seen in WT mice, The estradiol-treated ERKO mice failed, however, to manifest alterati ons in their thymic CD4/CD8 phenotypes compared with WT mice. Therefore, ER alpha is essential in nonhemopoietic cells to obtain a full-sized thymus, and ERalpha also mediates some of the response of the thymus to elevated es trogen levels. Finally, these results suggest that in addition to ER alpha, another receptor pathway is involved in estradiol-induced thymic atrophy.