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

Abstract

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.

Sox-4 Messenger RNA Is Expressed in the Embryonic Growth Plate and Regulated via the Parathyroid Hormone/Parathyroid Hormone-Related Protein Receptor in Osteoblast-like Cells

“…High expression of Sox‐4 mRNA in osteosarcoma cells and hypertrophic chondrocytes may suggest a role for Sox‐4 in maturation of osteoblasts and chondrocytes, analogous to what has been found for B cell and T cell development, where lack of Sox‐4 blocks further differentiation at the pro‐B cell stage (5) and restricts thymocyte differentiation (51) . Interestingly, Sox‐4 is highly expressed in the thymus, in which PTHrP and its receptor also is expressed (52) …”

Parathyroid Hormone-related Peptide (hPTHrP) and Parathyroid Hormone-related Peptide Receptor Type 1 (PTHR1) Expression in Human Thymus

“…Unlike rodent thymus (Funk et al 1999;Gunther et al 2000), human thymus expresses hPTHrP, but not PTH. This could be the result of the difference in embryological development in humans and rodents of the thymus and parathyroids.…”

“…In rodent thymus, both PTH (Gunther et al 2000) and PTHrP (Funk et al 1999) are expressed by the TEC component, whereas in the human thymus, only the presence of hPTHrP has been documented (Kramer et al 1991). At present, still unclear are which thymic cell components produce hPTHrP, as well as the possible role of hPTHrP and PTHR1 in human thymus physiology.…”