Expression of parathyroid hormone-related protein and the parathyroid hormone parathyroid hormone-related protein receptor in rat thymic epithelial cells

Thymic epithelial cells are an important source of cytokines and other regu latory peptides which guide thymocyte proliferation and maturation. Parathy roid hormone-related protein (PTHrP), a cytokine-like peptide, has been rep orted to affect the proliferation of lymphocytes in vitro. The studies pres ented here were undertaken to test the hypotheses that PTHrP is produced lo cally within the thymus where it could influence thymocyte maturation and, more specifically, that thymic epithelial cells (TEC) could be the intrathy mic source of PTHrP expression. To this end, immunohistochemical studies we re performed to localise PTHrP and the PTH/PTHrP receptor within the adult rat thymus. Antibodies directed against 2 different PTHrP epitopes, PTHrP(1 -34) and PTHrP(34-53), demonstrated prominent specific PTHrP immunoreactivi ty in both subcapsular and medullary TEC. In addition, faint but specific s taining for PTHrP was seen in the cortex, interdigitating between cortical lymphocytes while sparing epithelial-free subcapsular areas, thus suggestin g that cortical TEC could also be a source of PTHrP immunoreactivity. In co ntrast, PTH/PTHrP receptor immunoreactivity was only seen in medullary and occasional septal TEC; no evidence of cortical or lymphocytic PTH/PTHrP rec eptor immunoreactivity was detected. Immunohistochemical studies of culture d cytokeratin-positive rat TEC confirmed the results of these in situ studi es as cultured TEC were immunoreactive both for PTHrP and the PTH/PTHrP rec eptor. Thus these results demonstrate that PTHrP is produced by the epithel ial cells of the mature rat thymus. This suggests that PTHrP, a peptide wit h known cytokine, growth factor and neuroendocrine actions, could exert imp ortant intrathymic effects mediated by direct interactions with TEC, or ind irect effects on PTH/PTHrP receptor-negative thymocytes.