Thymic epithelial cells are an important source of cytokines and other regulatory peptides which guide
thymocyte proliferation and maturation. Parathyroid hormone-related protein (PTHrP), a cytokine-like
peptide, has been reported to affect the proliferation of lymphocytes in vitro. The studies presented here
were undertaken to test the hypotheses that PTHrP is produced locally within the thymus where it could
influence thymocyte maturation and, more specifically, that thymic epithelial cells (TEC) could be the
intrathymic source of PTHrP expression. To this end, immunohistochemical studies were 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
immunoreactivity in both subcapsular and medullary TEC. In addition, faint but specific staining for PTHrP
was seen in the cortex, interdigitating between cortical lymphocytes while sparing epithelial-free subcapsular
areas, thus suggesting that cortical TEC could also be a source of PTHrP immunoreactivity. In contrast,
PTH/PTHrP receptor immunoreactivity was only seen in medullary and occasional septal TEC; no evidence
of cortical or lymphocytic PTH/PTHrP receptor immunoreactivity was detected. Immunohistochemical
studies of cultured cytokeratin-positive rat TEC confirmed the results of these in situ studies as cultured
TEC were immunoreactive both for PTHrP and the PTH/PTHrP receptor. Thus these results demonstrate
that PTHrP is produced by the epithelial cells of the mature rat thymus. This suggests that PTHrP, a
peptide with known cytokine, growth factor and neuroendocrine actions, could exert important intrathymic
effects mediated by direct interactions with TEC, or indirect effects on PTH/PTHrP receptor-negative
thymocytes.