Widespread expression of the parathyroid hormone-related peptide and PTH/PTHrP receptor genes in intestinal epithelial cells

BACKGROUND: This study was designed to determine whether the genes for both parathyroid hormone-related peptide (PTHrP) and its receptor were expressed in close proximity to one another in various regions of the gut and whether they both were evident in two intestinal epithelial cell lines. The findings would test the idea that PTHRP acts as an autocrine or paracrine factor in the gut. EXPERIMENTAL DESIGN: Reverse transcription/PCR and Northern analysis were used to detect mRNA for PTHRP and its receptor in various regions of the normal rat gut, in epithelial cell populations isolated along the villus tip-crypt axis in rat jejunum, and in a rat and a human gastrointestinal epithelial cell line (IEC-6 and LoVo, respectively). Antisera to PTHRP also were used to detect the peptide in rat gastrointestinal tissues or in growth medium from cultured cells. RESULTS: Both PTHRP and PTHRP receptor mRNA were found in all regions of the rat gut, in all cell populations isolated from rat jejunum, and in the rat and human cell lines. Immunoreactive PTHRP in tissue sections was observed in rat jejunal epithelial cells all along the villus but not in crypt cells, and immunoreactive peptide was found in growth medium from the cultured intestinal epithelial cells. CONCLUSIONS: The results show that genes for PTHRP and its receptor are expressed widely in gut epithelia. Expression of the two genes in the same regions of the gut and in the same cell line implies a local autocrine/paracrine action of the peptide. Expression of the peptide in villus epithelium but not in crypt cells suggests a role in differentiating gastrointestinal epithelial cells.