The effect of sex steroids and hormonal contraceptives upon thymus and spleen on intact female rats.

In view of a possible influence on oral contraceptives upon the immune system, the effect of chronic treatment of intact adult female rats with sex steroids and contraceptive preparations upon the thymus and the spleen was investigated. Daily injections with 10 micrograms estradiol, estradiol benzoate, or diethyl stilbestrol for 2 weeks resulted in a marked but reversible involution of the thymus, while the spleen was not affected. Androgens exerted a significant effect at a dose of 0.3 mg, and progestogens only when 2 mg were given. When various contraceptive preparations were injected for 4 weeks, there was a total involution of the thymus which persisted even 2 weeks after cessation of treatment. The effect appeared to be mainly due to the estrogenic component. Progestogens intensified the reduction of thymic weight only at higher doses. Histological examinations revealed that estrogen treatment alone resulted in a reduction of the cortex and a depletion of lymphocytes. When contraceptive preparations were administered, the medulla was also reduced, and both cortex and medulla were replaced by reticular and adipose tissue. The estrogen receptors of thymus cytosol showed dissociation constants between 0.34 and 0.49 nM in diestrous rats, progesterone-treated rats and ovariectomized rats, and binding capacities between 6.5 and 2.6 fmoles/mg protein. It remains, however, to be shown whether the estrogen-induced involution of the rat thymus may lead to an impairment of immune responses.