Effect of 1,25-dihydroxyvitamin D3 on mouse thymus: role of extracellular calcium.
We recently reported that mice treated with 1,25-dihydroxyvitamin D3 ( 1,25-(OH)2D3) or 19-nor-1,25-(OH)2D2 experienced a severe loss of their thymocytes and decreased proliferation in response to concanavalin A mitogen. The present study investigated the effect of short-term treatment with 1,25-(OH)2D3 on the thymic architecture and thymocyte subsets. Daily treatment with 1,25-dihydroxyvitamin D3 at 20 ng per mouse for 4 days induced significant involution of thymic tissue. The atrophy was predominantly observed in the cortical component. Flow cytometric analysis of thymocyte subsets showed that the CD4 + CD8 + population was the primary target. Since the treated mice experienced profound hypercalcemia, we studied the effect of 1,25-(OH)2D3 on animals fed a vitamin D-deficient, low calcium diet or the same diet containing vitamin D for 25 days prior to treatment. The low calcium fed mice showed severe hypocalcemia and slight thinning of thymic cortex. Treatment with 1,25-(OH)2D3 moderately improved the hypocalcemia but had no further effect on the thymus of these animals. On the other hand, hypercalcemia and thymic atrophy were found in the animals fed the diet containing vitamin D. Overall, the atrophy effect on the thymus caused by 1,25-(OH)2D3 treatment was prevented by eliminating the hypercalcemia observed in + D + Ca treated animals. Thus, thymic atrophy probably resulted from hypercalcemia and not from 1,25-(OH)2D3 itself.
Mohamed
M I
MI
Department of Biochemistry, University of Wisconsin-Madison, WI, 53706, USA.
Beckman
M J
MJ
Meehan
J
J
DeLuca
H F
HF
D000818:Animals; D002117:Calcitriol / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D005434:Flow Cytometry; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D016176:T-Lymphocyte Subsets / Q000187:drug effects; D013950:Thymus Gland / Q000187:drug effects* / Q000276:immunology / Q000473:pathology
D003907:Dexamethasone; D002117:Calcitriol; D002118:Calcium