Interactions between the gonadal steroids and the immune system
Historically the fields of reproduction and immunology have been classified as separate biological disciplines. A connection between these fields was first reported in 1898 when Calzolari (1) observed that the thymus of rabbits castrated before sexual maturity was larger than that of the controls. At the time this report first appeared it was not considered of much importance. However, 70 years after Calzolari's publication, researchers have begun to place greater emphasis on the interactions between the reproductive and immune systems. These reproductive-immunological interactions appear to be hormonally regulated, and the hormones involved originate from the thymus, the hypothalamus-pituitary unit, and the gonads. In this article, the role of the gonadal steroids in regulation of the acquired immune system is emphasized.
In humans, the innate and acquired immune systems constitute the total immune system. The innate system (also known as the nonspecific system) encompasses all reactions that are not antigen dependent, such as phagocytosis and inflammation. The acquired system (also known as the specific system) involves the antigen-dependent reaction of classes of lymphocytes called T cells and B cells. T cells are regulators of the cell-mediated immune response, B-cell function, and phagocytosis, whereas B cells are involved in humoral immunity and produce immunoglobulins called antibodies (2, 3).
Both clinical and experimental evidence support the hypothesis that gonadal steroids regulate immune function. This conclusion is based on the following observations: (i) a sexual dimorphism exists in the immune response; (ii) the immune response is altered by gonadectomy and sex steroid hormone replacement; (iii) the immune response is altered during pregnancy when the amount of sex steroid hormone is increased; and (iv) the organs responsible for the immune response contain specific receptors for gonadal steroids. Sex Steroids and Humoral Immunity
Many studies have demonstrated that immunoglobin production is greater in females than in males. In mice, females show a greater and more sustained response than males to the antigens bovine serum albumin (4) and hemagglutinin (5), and females also generate higher titers of the immunoglobins IgG (6), IgG1 (7), IgM (6), and IgA (8) than do male controls. Female hamsters also generate larger amounts of immunoglobin as measured both in vitro (9) and in vivo (9, 10) than do males, and this lessening of antibody production in the male coincides with the increase in sex steroid hormones at sexual maturity (10).
The mechanism responsible for the greater concentrations of antibody in females than in males is not completely understood at present. However, estrogens enhance the antibody response in mice (11) and appear to regulate the synthesis of uterine IgA and IgG in rats (12). This suggests that the spontaneous increase of immunoglobin levels during the estrous cycle may result from the action of estradiol in the uterus (12).
One possible mechanism for the stimulation of antibody production by estrogen is found in a report by Paavonen et al. (13) suggesting that etradiol can inhibit suppressor T-cell activity. Since suppressor T cells prevent B cells from manufacturing antibody, it follows that inhibition of suppressor...