Distinct target cells and effects of 1 alpha,25-dihydroxyvitamin D3 and glucocorticoids in the rat thymus gland.
Thymocytes are known to possess receptors for glucocorticoids (GC) as well as for alpha, 25-dihydroxyvitamin D3 [1,25-(OH)2D3]. We have now investigated the distribution of the receptors for GC and 1,25-(OH)2D3 in rat thymocytes and compared the effects of the two steroid hormones on short term primary cultures of these cells. We report that in thymic cells, as in other tissues, 1,25-(OH)2D3 and GC bind specifically to distinct receptor molecules which exhibit sedimentation coefficients of 3.3S and 3.7S, respectively. Furthermore, the thymocytes that express the 1,25-(OH)2D3 receptor belong to a different and distinct subpopulation than the cells that express the glucocorticoid receptor. Specifically, by separating the thymocytes into two subsets by means of agglutination with the lectin peanut agglutinin (PNA), we have determined that the 1,25-(OH)2D3 receptor-positive cells belong to the PNA-negative medullary mature subset, whereas the GC receptor-positive cells belong to the PNA-positive cortical immature subset of thymocytes. Finally, we have compared the effects of the two steroid hormones on primary cultures of each of the two subsets as well as on unseparated thymocytes and found that GC act on PNA-positive cells to induce cell lysis; this leads to an enrichment in 1,25-(OH)2D3 receptor-positive thymocytes, as indicated by an apparent increase (6-fold) in the 1,25-(OH)2D3 binding in the cells surviving at the end of the culture. In contrast, we found that 1,25-(OH)2D3 acts on the PNA-negative cells to decrease the rate of cell lysis. These data indicates that the target cells for GC and 1,25-(OH)2D3 in the thymus are distinct and that these two hormones exert a different regulatory influence on the gland.
Provvedini
D M
DM
Section of Endocrinology/Metabolism, Veterans Administration Medical Center, Indianapolis, Indiana 46202.
Sakagami
Y
Y
Manolagas
S C
SC
D000818:Animals; D002117:Calcitriol / Q000378:metabolism / Q000494:pharmacology*; D002469:Cell Separation; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002499:Centrifugation, Density Gradient; D005938:Glucocorticoids / Q000494:pharmacology*; D037102:Lectins / Q000378:metabolism; D008297:Male; D019887:Peanut Agglutinin; D051381:Rats; D018167:Receptors, Calcitriol; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D011987:Receptors, Steroid / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D014222:Triamcinolone Acetonide / Q000378:metabolism / Q000494:pharmacology
D005938:Glucocorticoids; D037102:Lectins; D019887:Peanut Agglutinin; D018167:Receptors, Calcitriol; D011965:Receptors, Glucocorticoid; D011987:Receptors, Steroid; D014222:Triamcinolone Acetonide; D002117:Calcitriol