Estrogen and antiestrogen effects on different lymphoid cell populations in the developing fetal thymus of guinea pig

Estrogen responsiveness in the developing fetal thymus of guinea pig has been investigated. One-day estradiol (E2) treatment (1 mg/kg BW) of pregnant animals selectively decreases the number of larger lymphoid cells of the outer cortex of the fetal thymus, without affecting the global number of cortical lymphocytes. E2 treatments for longer periods (from 2 until 6 days) provoke a further impairment in the pattern of outer cortical lymphocytes, selectively reducing larger lymphoid cells, and also decrease the global number of cortical lymphocytes without affecting medullary lymphocytes. Treatment with the antiestrogen tamoxifen (2 mg/kg BW . day for 6 days) results in a transfer of cytoplasmic estrogen receptor to the nuclei of fetal thymus and also affects the histology of the fetal organ, although to a lesser extent than E2. However, when tamoxifen is administered with E2 (1 mg/kg BW . day during the last 3 days of tamoxifen treatment), it antagonizes all of the effects induced by E2 alone on the fetal thymus. The 6-day E2 treatment decreases the weight of the fetal thymus in an age-dependent manner; this effect is progressively more intense from 42 days of gestation at the time of treatment (mean +/- SE, 25 +/- 5% decrease) up to the end of gestation (63 +/- 7% decrease). The effect of E2 on large lymphoid cells also increases in an age-dependent manner. The extent of the estrogen responses observed is correlated with the levels of cytoplasmic estrogen receptors, which increase from 38 days to the end of gestation. The intracellular compartmentalization of estrogen receptor shows that cytoplasmic estrogen receptors are transferred to the nuclei by E2 at both younger and older ages. It is concluded that E2 has differential actions on the lymphoid cell population of the fetal thymus of guinea pig by events antagonized by the antiestrogen tamoxifen and related to the availability and development of cytoplasmic estrogen receptors.