Growth and maintenance of the mouse adrenal cortex

Abstract

The adrenal cortex is classically divided into three morphologically and biochemically distinct zones, covered by a thin, cellular capsule. The adult adrenal cortex is a dynamic tissue in which distinct regions of cell proliferation, movement and death have been identified. Several models for stem cell maintenance of the adult adrenal cortex have been proposed, but adrenocortical stem cells have not yet been identified. Adrenal cortices of 21OH/LacZ transgenic mice show similar mosaic patterns of β-galactosidase staining to X- inactivation mosaics and LacZ ↔ wildtype chimeras. 21OH/LacZ mice provide a tool for lineage analysis, which may help to i) identify clones of cells produced by stem cells in the adult, ii) determine when stem cells begin to function and iii) evaluate different models of how stem cells maintain the adrenal cortex. Analysis of 21OH/LacZ transgenic adrenal cortices showed that the randomly orientated clusters of fetal patches change progressively during the perinatal period to adult radial stripes. Correlation of changes in mosaic patterns and the locations of cell proliferation suggests that the stripes arise by edge-biased growth during the perinatal growth period. Although stem cells may not be involved in the initial formation of stripes, it seems likely that stem cells later maintain the stripes by producing clones of cells that move centripetally to displace the earlier fetal patterns and later replace aging cells. Various combinations of BrdU labelling and chase periods demonstrated that most cell division occurred in the outer 40% of the adrenal cortex, confirmed that cells moved towards the medulla and identified a population of label-retaining cells near the capsule, which could include stem cells. (Stem cells have been recognised as BrdU label-retaining cells in other tissues because they divide less frequently than their daughter cells so dilute the incorporated BrdU more slowly.) Stripe patterns in adult 21OH/LacZ transgenic adrenal cortices were examined to try to distinguish between various models proposed for stem cell maintenance of the adrenal cortex. The observed continuous radial stripe pattern favours the general hypothesis that a single population of stem cells in the periphery maintains the entire adrenal cortex, although other explanations are possible. Quantitative analysis of adult stripe patterns did not show the reduction in stripe number that might be predicted if an age-related decline in adrenocortical stem cell function occurs, as may happen in some other tissues.