Effect of thymosin on glucocorticoid receptor activity and glucocorticoid sensitivity of human thymocytes.
Incubation with thymosin fraction 5, (TMS F5 at 300 micrograms/ml) a partially purified thymic factor, reduced the steroid binding activity of human infant thymocytes from 9.6 +/- 2.1 fmole/ml to 5.0 +/- 2.0 fmole/ml. The glucocorticoid receptor activity in normal infant thymocytes was found to be 2,146 +/- 726 (s.d.) sites per cell with dissociation constant of 1.4 +/- 0.6 X 10(-8)M. TMS F5 also increased the resistance of human thymocytes to the cytolytic effect of dexamethasone (2.5 X 10(-8)M) to 168.6 +/- 30.2% of control (P less than 0.01). In animals, medullary and peripheral blood T cells are more resistant to glucocorticoids than immature thymic T cells. The results show that thymosin can induce changes consistent with differentiation in human thymocytes. These in vitro results are consistent with a physiological role of thymosin in intrathymic T cell maturation in man. Incubation of a human malignant thymus derived T cell line (MOLT 3) with TMS F5 also resulted in a significant reduction of the number of steroid binding sites to 44.2 +/- 15.3% of control (P less than 0.05), but TMS F5 did not significantly reduce the glucocorticoid sensitivity of MOLT 3 cells.
D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002675:Child, Preschool; D003907:Dexamethasone / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007223:Infant; D007945:Leukemia, Lymphoid / Q000276:immunology; D011965:Receptors, Glucocorticoid / Q000187:drug effects*; D011987:Receptors, Steroid / Q000187:drug effects*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism; D013947:Thymosin / Q000031:analogs & derivatives* / Q000494:pharmacology
D011965:Receptors, Glucocorticoid; D011987:Receptors, Steroid; C033782:thymosin fraction 5; D013947:Thymosin; D003907:Dexamethasone; D013936:Thymidine