Fig. 5.

The effects of PGE₂ are mediated through transactivation of the epidermal growth factor receptor (EGFR). Tamoxifen treatment of EGFR^f/fVil-Cre/ERT2 mice from age 7 days to age 14 days resulted in depletion of the EGFR in intestinal epithelial cells. These mice had reduced frequency of crypt fission (A), fewer numbers of Lgr5⁺ crypt epithelial cells (B), and reduced Lgr5⁺ crypt epithelial stem cell proliferation (C) compared with control mice. D: positional distribution of 5-bromo-2-deoxyuridine (BrdU)-labeled intestinal crypt epithelial cells in 14-day-old EGFR^f/fVil-Cre/ERT2 mice. The highest rate of epithelial cell proliferation in control mice was in the range of position 4 to position 8. Tamoxifen treatment resulted in significantly decreased positional epithelial proliferation in the lower one-half of the crypt compared with controls. 16,16-Dimethyl PGE₂ (dmPGE₂) treatment of mice having tamoxifen-induced depletion of EGFR failed to rescue crypt epithelial proliferation. Tamoxifen treatment had no effect on crypt epithelial proliferation in EGFR^f/f mice, which are functionally the same as wild-type (WT) mice and responded to dmPGE₂ treatment with increased crypt epithelial proliferation. Values are means ± SE for 8–15 mice/treatment group. *P < 0.05, **P < 0.01, and ***P < 0.001 compared with control mice.