Endocrine Abstracts

JOINT3744

Chronic stress is a pervasive concern in the modern society. The HPA axis dysregulation in chronic stress and psychiatric disorders is tightly linked with hypertrophy and hyperplasia of the adrenal gland. These stress-induced cellular adaptations might employ and could be a result of capsular progenitor behaviour. However, little is known about the contribution of resident progenitor cells to these stress-induced cellular changes. In this study, we aim to unravel the mechanisms involved in the regulation of adreno-capsular progenitors during acute and repeated restraint stress. To that aim, we used a tamoxifen inducible Gli1:CreERT2/R26R:eYFP mouse line to lineage trace and monitor Gli1⁺ adrenocortical progenitors during restraint stress in the adult adrenal cortex in vivo using both sexes. Our results reveal migratory patches of Gli1⁺ spindle-like cells towards zona glomerulosa (zG) in the cortex of stressed male mice. These patches resemble the adrenocortical neoplasms previously described in literature and express GATA4, a common marker of the adrenogonadal primordium. Further, significant upregulation of the capsular markers Nr2f2 and Rspo3, a signaling molecule involved in the control of cell renewal in the tissue, was noted in the adrenal cortex of those mice. Concerning female mice, it is already known that Gli1⁺ cells contribute to the tissue renewal under homeostatic conditions. Preliminary results suggest that the subcapsular patches of Gli1⁺-derived eYFP⁺ cells are rather reduced in the cortex of stressed female mice compared to the control group. Overall, this may suggest that in female mice the process of capsular progenitor cell recruitment is reduced when the need for increased steroid production occurs. Notably, beside the reduced recruitment of capsular progenitor cells, we additionally observed significant upregulation of Cyp11b2, Dab2 and the Wnt target Lef1, which may indicate a higher response of the zG in female compared to male mice. Lastly, our preliminary results from single-cell RNA sequencing data from stressed and non-stressed mice from both sexes confirm the sexually dimorphic response of the capsule during restraint stress. By further analysing these data, we aim to shed light on molecular factors involved in the paracrine communication between the capsule and the rest of the cortex in stress that could potentially regulate directly or indirectly the stress response and the steroid production.