Functional Zonation of the Adult Mammalian Adrenal Cortex

Abstract

The standard model of adrenocortical zonation holds that the three main zones, glomerulosa, fasciculata, and reticularis each have a distinct function, producing mineralocorticoids (in fact just aldosterone), glucocorticoids, and androgens respectively. Moreover, each zone has its specific mechanism of regulation, though ACTH has actions throughout. Finally, the cells of the cortex originate from a stem cell population in the outer cortex or capsule, and migrate centripetally, changing their phenotype as they progress through the zones. Recent progress in understanding the development of the gland and the distribution of steroidogenic enzymes, trophic hormone receptors, and other factors suggests that this model needs refinement. Firstly, proliferation can take place throughout the gland, and although the stem cells are certainly located in the periphery, zonal replenishment can take place within zones. Perhaps more importantly, neither the distribution of enzymes nor receptors suggest that the individual zones are necessarily autonomous in their production of steroid. This is particularly true of the glomerulosa, which does not seem to have the full suite of enzymes required for aldosterone biosynthesis. Nor, in the rat anyway, does it express MC2R to account for the response of aldosterone to ACTH. It is known that in development, recruitment of stem cells is stimulated by signals from within the glomerulosa. Furthermore, throughout the cortex local regulatory factors, including cytokines, catecholamines and the tissue renin-angiotensin system, modify and refine the effects of the systemic trophic factors. In these and other ways it more and more appears that the functions of the gland should be viewed as an integrated whole, greater than the sum of its component parts.

Human Adrenal Cortex: Epigenetics and Postnatal Functional Zonation

“…Nevertheless, evidence from animal studies favors the progenitor cell proliferation/migration hypothesis [7]. This theory proposes that the cortical cells originate from a stem cell population in the outer cortex or capsule, and migrate centripetally becoming functionally differentiated in the appropriate zonal environment [1, 5, 7]. In agreement with the migration model, the cell proliferation index is highest in the outer ZG of human adrenal tissues from early infancy to late puberty [8].…”

“…The origin and maintenance of the adrenocortical zones have been debated over the years. Nevertheless, evidence from animal studies favors the progenitor cell proliferation/migration hypothesis [7]. This theory proposes that the cortical cells originate from a stem cell population in the outer cortex or capsule, and migrate centripetally becoming functionally differentiated in the appropriate zonal environment [1, 5, 7].…”

Adrenal cortical and chromaffin stem cells: Is there a common progeny related to stress adaptation?

“…A close morphological and functional interdependence of cortical and chromaffin cells has already been demonstrated (reviewed in (Ehrhart- Bornstein and Bornstein, 2008)). In fact, it becomes more and more clear that the functions of the adrenal gland should be viewed more as an integrated whole greater than the sum of its parts (Haase et al, 2011;Vinson, 2016).…”

Molecular Mechanisms of Stem/Progenitor Cell Maintenance in the Adrenal Cortex

“…This idea was first hypothesized in the 19th century, based on histological observations of gradual changes in morphology observed in cells between the capsule and the medulla (32, 33) [reviewed in Ref (34)]. Over the years, different studies have shown that, under physiological conditions, proliferating cells are located preferentially in the outermost layers of the cortex, in the subcapsular region (35, 36).…”