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.