title: Age/sex dependent and non-monotonous dose-response effect of diethylstilbestrol on the immune functions in mice.
abstract: High amounts of estrogens are known to suppress immune functions in both human and animal models. Our supportive data is that the immune functions were activated by gonadectomy in young adults mice. However, recent reports indicate that estrogen is required for the normal development of thymus. These findings lead us to an assumption that sex hormone status induces much more complex effects on immune functions depending on the host age/sex and dose ranges. Here, low doses of DES (diet containing 0.4 or 4.0 microg/kg diet) were given for 2 months to young adult and aged C57BL/6 mice, and thymic and splenic parameters including flow-cytometric subpopulation analyses, mitogenic responses and NK activity were monitored. This study revealed that the low dose effects of exogenous estrogen are strongly dependent on the age and sex of the recipients and many parameters show non-monotonous dose response effect. In conclusion, effect of exogenous estrogens on immune functions should be assessed for all age and sex, and in expectation of non-monotonous dose-response relationship.
authors.affiliation: Department of Pathology and Immunology, Aging and Developmental Sciences, Tokyo Medical and Dental University Graduate School, 1-5-45 Yushima, Bunkyo-ku, 113-8519, Tokyo, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Utsuyama
authors.forename: Jun
authors.initials: J
authors.lastname: Kanno
authors.forename: Tohru
authors.initials: T
authors.lastname: Inoue
authors.forename: Katsuiku
authors.initials: K
authors.lastname: Hirokawa
mesh_terms: D000367:Age Factors; D000818:Animals; D004054:Diethylstilbestrol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D011960:Receptors, Estrogen / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012737:Sex Factors; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004968:Estrogens, Non-Steroidal; D011960:Receptors, Estrogen; D004054:Diethylstilbestrol