Estrogen effects on lymphoid tissue in neonatal and adult female mice

Outbred female mice of the NMRI strain were treated with daily doses of diethylstilbestrol (DES; 0.1-10 micrograms), estradiol-17 beta (E2; 5 micrograms), testosterone (T; 5 or 25 micrograms), progesterone (P; 100 micrograms), corticosterone (CC; 10 or 50 micrograms), or olive oil (controls) for the first 5 days after birth. Animals were killed on day 6 after birth, at 2, 4, and 8 weeks or at 4 and 6 months. Only CC resulted in reduced thymus index weight (IW, mg organ weight/g body weight) on day 6 while the estrogen-induced reduced IW was secondary to a reduced body weight. Four-week-old and older estrogen-treated females had increased thymus IW (1.8-fold at 8 weeks after 5 micrograms DES/day neonatally) which was still seen at 6 months. Estrogen-induced thymus enlargement also occurred in 8-week-old inbred NMRI females and in females belonging to the BALB/c strain. Thymus IW in 8-week old T-, P- and CC-treated females was as in controls. The leukocyte counts in blood and bone marrow were lower in DES females than in controls. The responses (thymus IW, peripheral blood leukocyte count) of 8-week-old females to ovariectomy and challenge with DES were different in DES females and in control females. The mitogen response of spleen lymphocytes and thymocytes was similar in controls and DES females. An anomaly in the hypothalamic-pituitary-gonad-thymus axis of adult, neonatally estrogen-treated females might explain the thymus enlargement.