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 wer e expressed in close proximity to one another in various regions of th e gut and whether they both were evident in two intestinal epithelial cell lines. The findings would test the idea that PTHrP acts as an aut ocrine or paracrine factor in the gut. EXPERIMENTAL DESIGN: Reverse tr anscription/PCR and Northern analysis were used to detect mRNA for PTH rP and its receptor in various regions of the normal rat gut, in epith elial cell populations isolated along the villus tip crypt axis in rat jejunum, and in a rat and a human gastrointestinal epithelial cell li ne (IEC-B and LoVo, respectively). Antisera to PTHrP also were used to detect the peptide in rat gastrointestinal tissues or in growth mediu m from cultured cells. RESULTS: Both PTHrP and PTHrP receptor mRNA wer e found in all regions of the rat gut, in all cell populations isolate d from rat jejunum, and in the rat and human cell lines. Immunoreactiv e PTHrP in tissue sections was observed in rat jejunal epithelial cell s all along the villus but not in crypt cells, and immunoreactive pept ide was found in growth medium from the cultured intestinal epithelial cells. CONCLUSIONS: The results show that genes for PTHrP and its rec eptor are expressed widely in gut epithelia. Expression of the two gen es 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 pep tide in villus epithelium but not in crypt cells suggests a role in di fferentiating gastrointestinal epithelial cells.