Adrenocorticotropic tumor cells transplanted into mouse embryos affect pancreatic histogenesis

A wide range of individual differences exist in the total number of functional and structural units in each organ, such as β cells in pancreatic islands, and these units are the basis of the organ's overall function, including its functional reserve. The endocrine environment may influence organ histogenesis, during which functional and structural units are formed and increase in number. We analyzed the effects of a continuous high level of adrenocorticotropic hormone (ACTH) and/or secondarily induced glucocorticoid on histogenesis of the pancreas in mouse embryos. Pituitary tumor-derived AtT20 cells, which secrete ACTH continuously, were injected subcutaneously into mouse embryos at embryonic day (E) 12.5, and the embryos were allowed to develop exo utero until E18.5 (AtT20 group). E18.5 AtT20 group embryos with high ACTH levels (23.74 ± 6.19 ng/mL vs control group, 0.48 ± 0.40 ng/mL, P < 0.05) were examined for the effects on histogenesis of the pancreas. Using serial sections of the E18.5 pancreas, we stereologically measured the volumes, and counted total cell numbers and numbers of mitotic or pyknotic cells of the whole pancreas, endocrine and exocrine cells, and glucagon-immunopositive α cells and insulin-immunopositive β cells in the endocrine part. Although the volumes of the whole pancreas and exocrine part did not change significantly, in the AtT20 group the endocrine part was significantly larger, with fewer pyknotic cells and lower ratios of α and β cells than in the control group. These results suggest that the high level of ACTH and/or glucocorticoid affects histogenesis of the pancreas.