Role of Parathyroid Hormone/Parathyroid Hormone-Related Peptide on Cell Proliferation in the Gastric Mucosa

Parathyroid hormone-related peptide (PTHrP) is widely expressed in normal tissues and elicits various functions through the PTH/PTHrP receptor. Relaxation effects of PTHrP on gastrointestinal smooth muscle cells were well documented, but the physiological role on mucosal growth and differentiation is little known. The purpose of this study was to evaluate the expression of PTHrP and PTHPTHrP receptor in the rat gastric mucosa, and the role of PTHrP on mucosal cell proliferation. Male Wistar rats were used in this study. Localization of PTHrP and PTH/PTHrP receptor were observed by immunohistochemistry and in situ hybridization. Expression of PTH/PTHrP receptor mRNA were examined by RNase protection assay in control and stress condition. Double staining with BrDU incorporation was performed to differentiate cell cycle states. Cell proliferative effect by external PTHrP-(1-34) was evaluated by BrDU incorporation. PTHrP immunopositive cells were encountered in and around the mucosal neck area. PTH/PTHrP receptor immunoreactivity was observed in the gastric mucosa broadly. Cells with stronger expression for PTHrP and its cognate receptor were located in the vicinity of generative zone. But BrDU incorporating cells were negative for both PTHrP and PTH/PTHrP receptor. By RNase protection assay, PTH/PTHrP receptor mRNA expression was weak in a steady state, and the receptor expression increased at stress. External PTHrP-(1-34) did not show cell proliferative effect in a steady state. At stress BrDU incorporation was suppressed significantly, and PTHrP-(1-34) increased BrDU incorporation. These observations suggest that PTHrP and PTH/PTHrP receptor involve maintenance of mucosal growth and differentiation in the stomach