Neonatal estrogen treatment and its consequences for thymus development, serum level of autoantibodies to cardiolipin, and the delayed-type hypersensitivity response.
Eight-week-old female and male NMRI mice treated neonatally with the synthetic estrogen diethylstilbestrol (DES), estradiol-17beta, or tamoxifen displayed an enlarged thymus when compared with controls (approximately 1.5-fold). In control females, either ovariectomy or adrenalectomy increased thymus weight to the level characteristic for DES-treated females, but these endocrine ablations had no significant effect in DES females. The serum estrogen levels were similar in intact DES, ovariectomized DES, and ovariectomized female controls; serum corticosterone was similar in controls and DES females. The expression of the Thy1.2+ marker and the percentages of CD4+CD8+ DP and CD4+ and CD8+ SP cell subsets were similar in thymocyte populations from 8-wk-old controls and DES females; the CD4+ and CD8+ SP subsets were similar in splenocyte populations. The levels of serum immunoglobulin (Ig) G and IgM autoantibodies to cardiolipin showed age-dependent fluctuations but were similar in controls and DES females; however, the IgG autoantibodies in DES females were qualitatively different from those in controls with respect to sensitivity to bovine serum (a source of beta2-glycoprotein I). Contrary to females, DES-treated males had higher levels of autoantibodies than controls. The delayed-type hypersensitivity (DTH) response to oxazolone was similar in controls and DES animals at 8 wk, increased in DES females and males at 6 mo, but was reduced in DES females at 1 yr. Thus, even though adult mice with thymus enlargement after neonatal estrogen treatment do not differ from controls with respect to the expression of the Thy1.2 marker or percentages of CD4+/CD8+ DP or SP subsets in thymus and spleen, qualitative and quantitative differences occur in immune parameters (autoantibodies to cardiolipin) and a T-cell-dependent immune response (DTH).
Forsberg
J G
JG
Tornblad Institute, University of Lund, Sweden. John-Gunnar.Forsberg@anatom.lu.se
D000315:Adrenalectomy; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D017153:Antibodies, Anticardiolipin / Q000032:analysis / Q000187:drug effects*; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes; D004054:Diethylstilbestrol / Q000494:pharmacology / Q000633:toxicity*; D004958:Estradiol / Q000494:pharmacology / Q000633:toxicity*; D004965:Estrogen Antagonists / Q000494:pharmacology / Q000633:toxicity*; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology / Q000633:toxicity*; D005260:Female; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D007074:Immunoglobulin G / Q000032:analysis; D007075:Immunoglobulin M / Q000032:analysis; D016131:Lymphocyte Subsets; D008297:Male; D051379:Mice; D010052:Ovariectomy; D013629:Tamoxifen / Q000494:pharmacology / Q000633:toxicity*; D013950:Thymus Gland / Q000033:anatomy & histology / Q000187:drug effects*
D017153:Antibodies, Anticardiolipin; D004965:Estrogen Antagonists; D004968:Estrogens, Non-Steroidal; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D013629:Tamoxifen; D004958:Estradiol; D004054:Diethylstilbestrol