Role of oestrogen receptors alpha and beta in immune organ development and in oestrogen-mediated effects on thymus.
Oestrogens affect the development and regulation of the immune system. To determine the role of oestrogen receptors alpha (ER-alpha) and beta (ER-beta) on the development of the immune system, male ER-alpha (ERKO) and ER-beta (BERKO) mice, as well as alphabeta-double knockout (DERKO) mice, were studied. Deletion of ER-alpha led to hypoplasia of both thymus and spleen. Interestingly, a higher frequency of immature double CD4+ CD8+ thymocytes was found in ER-alpha(-) mice compared with ER-alpha(+) mice. Female oophorectomized BERKO mice given oestradiol (E2) displayed a similar degree of thymic atrophy compared with the wild-type strain but showed only limited involution of thymus cortex and no alteration of thymic CD4/CD8 phenotype expression. Our data demonstrate that expression of ER-alpha, but not ER-beta, is mandatory in males for development of full-size thymus and spleen, whereas expression of ER-beta is required for E2-mediated thymic cortex atrophy and thymocyte phenotype shift in females. A potential background for the above findings may be down-regulated activity in the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis in males lacking ER-alpha and suppressed sensitivity of females lacking ER-beta to E2-mediated suppression of IGF-1.
Erlandsson
M C
MC
Department of Rheumatology, University of Göteborg, Sweden. erlandsson@rheuma.gu.se
Ohlsson
C
C
Gustafsson
J A
JA
Carlsten
H
H
D000818:Animals; D001284:Atrophy / Q000139:chemically induced; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens / Q000502:physiology*; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011960:Receptors, Estrogen / Q000235:genetics / Q000502:physiology*; D013154:Spleen / Q000254:growth & development* / Q000473:pathology; D013950:Thymus Gland / Q000254:growth & development* / Q000276:immunology / Q000473:pathology
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D011960:Receptors, Estrogen; D004958:Estradiol; D007334:Insulin-Like Growth Factor I