Mitoses of existing corticotrophs contribute to their proliferation in the rat pituitary during the late fetal period.

We studied the proliferation of pituitary corticotrophs quantitatively by labeling the proliferating cells with bromodeoxyuridine (BrdU) and carrying out immunocytochemistry for ACTH in rat fetuses at 19.5 days of gestation. In addition to labeling proliferating cells with a single injection of BrdU, we used double BrdU administrations at 9:00 and 19:00 for a more sensitive detection of proliferating cells. With this double administration, the number of cells labeled with either BrdU or both BrdU and ACTH increased by 1.75 and 2.3 times, respectively, compared with the single BrdU injection. The labeled cells further increased when the sections were stained for the proliferating cell nuclear antigen (PCNA) instead of BrdU. The number of cells labeled with PCNA or both PCNA and ACTH was 1.37 and 1.68 times that of the cells labeled with either BrdU or both BrdU and ACTH, respectively. The ratio of BrdU/ACTH-labeled cells or PCNA/ACTH-labeled cells to all corticotrophs was 13.6% and 24.3%, respectively, much higher than the ratios in fetuses having a single BrdU injection (6.6%). These results indicate that the mitosis of existing corticotrophs contributes greatly to their increase during the late fetal period.