Short-term and long-term effects of estrogen on lymphoid tissues and lymphoid cells with some remarks on the significance for carcinogenesis.

Estrogens have long been thought to play a role in regulating the immune system. The difference in some types of immune responses between males and females is well-known, as is the pronounced thymic involution induced by exogenous estrogens. Estrogens stimulate some aspects of macrophage activity and, depending on dose and mitogen, inhibit or stimulate lymphocyte proliferative response in vitro. Another example is the estrogen effect on the delayed type hypersensitivity response. A broad review is given of such estrogen effects on lymphoid tissue and immune response. Most of the studies published so far are phenomenological. However, the recent description of estrogen receptors in the thymus and in some lymphocyte subpopulations, as well as a deeper understanding of regulating factors in the immune system, open the possibility of a more detailed understanding of the estrogen mechanism of interference. Estrogen effects in adults are reversible. After treating neonatal mice with the synthetic estrogen diethylstilbestrol (DES), disturbances are induced in lymphocyte populations and lymphocyte functions which are permanent and irreversible. Lymphocytes from adult, neonatally DES-treated female mice have a reduced mitogen response to ConA and LPS (T and B cell mitogen) and the delayed type hypersensitivity response is depressed. A detailed analysis demonstrated a decreased T helper cell population. The activity of Natural Killer cells is permanently reduced and this functional impairment is related to a decreased number of these cells, in turn determined at the bone marrow level. The same animals have an increased sensitivity to chemical carcinogens (methylcholanthrene) and they spontaneously develop epithelial changes in the uterine cervix which morphologically are similar to adenocarcinoma. The association between estrogen-associated malignancy and estrogen effects in lymphocyte functions deserves further study.