Daily regeneration of rat adrenocortical cells: Circadian and zonal variations in cytogenesis

Daily regeneration of rat adrenocortical cells were investigated in terms o f circadian and zonal variations by following the cells at the DNA-synthesi zing stage. An S-phase was assessed by 5-bromo-2'-deoxyuridine (BrdU) incor poration into the cell-nuclei and/or by visualizing proliferating cell nucl ear antigen. The BrdU-positive cells were observed throughout the day mainl y in two regions of the adrenal cortex, i.e. the innermost portion of the z ona glomerulosa and the outermost portion of the zona fasciculata. Cells on ly in a latter region showed a distinct circadian rhythm of cell proliferat ion with a peak at 3-4 a.m. A remarkable rise in the plasma adrenocorticotr opin (ACTH) concentration preceded such an increase in the cell proliferati on by about 4 hours. This phenomenon could be mimicked by raising the plasm a ACTH concentration by the administration of Cortrosyn Z or metyrapone. An giotensin II-stimuli induced by Na-deficiency increased the proliferation o f zona glomerulosa cells in the former region at 6-7p.m without significant effects on that of the zona fasciculata cells in the latter region. Thus a t least two sites, which respond differentially to the day/night cycle and circulating hormone levels, exist in rat adrenal cortex being responsible f or the cytogenesis in this endocrine organ.