Estrogen immunosuppression is regulated through estrogenic responses in the thymus.

Abstract

Previous studies have clearly established that physiologic and pharmacologic levels of estrogens modulate immunologic responses that result in simultaneous activation of the reticuloendothelial system and depression of cell-mediated immunity. The mechanisms of estrogen immunoregulation were examined in adult female mice administered pharmacologic levels of exogenous estrogens. Evaluation of steroidal and nonsteroidal compounds with varying degrees of estrogenicity (i.e., uterotrophic activity) provided evidence that their immunotoxicity, for the most part, correlates with estrogenicity. The mechanisms responsible for these effects appear to be complex, mediated through a direct chemical interaction with lymphoid target cells, as well as with nonlymphoid tissue, resulting in the release of soluble immunoregulatory factors. The latter phenomenon was examined in detail and it appears to constitute a regulatory factor(s) produced by thymic epithelium in response to an estrogen stimulus. This response is not only estrogen specific but may involve specific binding to estrogen receptors or receptor-like structures present in cytosol preparations from thymic epithelial cells.