The contribution of capsular and subcapsular progenitor cells in homeostatic adrenal cortex self-renewal and zonal-specific remodelling.

The onset of menopause in women, the decrease in testosterone secretion in men after the age of 40 and the decrease in production of growth hormone from the brain are well-recognised biological changes affecting our endocrine system as we age.
The adrenal glands are two small organs located on top of the kidneys. The outer part of each gland, called the adrenal cortex, is essential for life, as it is the main site of production of steroid hormones. These steroid hormones affect carbohydrate metabolism and control the stress response, control blood volume and salt balance, and influence blood pressure.
The adrenal cortex "reproduces itself" over time (a process called self-renewal), and a group of cells (called stem cells) which we have identified in the outermost layers of the gland are responsible for generating new steroid-producing cells throughout our lifetime. The aging adrenal is a poorly investigated area, despite the importance of the gland in human health and disease. Even less, the contribution of stem cells to the generation of new hormone-producing cells during our lifetime is entirely unknown. With this proposal we aim at determining differences in the ability of adrenal stem cells to make new steroid-producing cells between young and adults, males and females, with a particular emphasis on cells which produce the hormones aldosterone and corticosterone.

The adrenal cortex is an essential endocrine organ that undergoes constant self-renewal; new cells are continuously generated in the capsular/subcapsular region of the gland and these cells support the centripetal streaming and lineage conversion to functional steroid-producing cells in the cortex, up to senescence and cell death cells at the cortex/medulla boundary. This proposal aims at understanding how adrenocortical stem/progenitor cells contribute to the gland self-renewal during the lifecourse, using genetic lineage tracing of adrenocortical progenitor cells in the young and aged experimental animal. We will also include a regimen aimed at expanding and retracting the aldosterone-producing zona glomerulosa, and investigate the fate of mature aldosterone-producing cells once no longer required. Moreover, we will assess the contribution of adrenocortical progenitor cells during the regeneration of the zona fasciculata after dexamethasone treatment. Therefore, this study will uncover the contribution of two stem cell populations during physiological self-renewal as well as remodelling following physiological (dietary) and pharmacological (ACE-inhibitors, glucocorticoids) interventions, in both the young and old experimental animal.