Age-related synthesis of glucocorticoids in thymocytes.
Glucocorticoids (GCs) are primarily synthesized in the adrenal glands but an ectopic production has also been reported in the brain, the gastrointestinal tract and in thymic epithelial cells (TEC). Here we show that thymocytes express genes encoding for all enzymes required for de novo GC synthesis and produce the hormone as demonstrated by both a GC specific reporter assay and a corticosterone specific ELISA assay. Interestingly, GC synthesis is detectable in cells from young mice (4 weeks) and thereafter increases during aging (14-22 weeks) together with an increased gene expression of the rate-limiting enzymes StAR and CYP11A1. Hormone production occurred at a thymocyte differentiation stage characterized by being double positive for the CD4 and CD8 surface markers but was found to be unrelated to CD69 expression, a marker for thymocytes undergoing positive selection. No GC synthesis was found in resting or anti-CD3 activated CD4 and CD8 positive T cells isolated from the spleen. Thymocyte-derived GC had an anti-proliferative effect on a GR-transfected cell line and induced apoptosis in thymocytes. The age- and differentiation stage-related GC synthesis in thymocytes may play a role in the involution process that the thymus gland undergoes.
Qiao
Shengjun
S
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 171 77 Stockholm, Sweden. Shengjun.Qiao@ki.se
Chen
Liying
L
Okret
Sam
S
Jondal
Mikael
M
D000375:Aging / Q000502:physiology*; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D020869:Gene Expression Profiling; D017930:Genes, Reporter; D005938:Glucocorticoids / Q000096:biosynthesis*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000166:cytology; D013950:Thymus Gland / Q000166:cytology / Q000378:metabolism
D015703:Antigens, CD; D015415:Biomarkers; D005938:Glucocorticoids