The densities of zona glomerulosa and fasciculata cells of rat adrenals were found to be 1.072 ± 0.004 and 1.040 ± 0.001 respectively. doi: 10.1038/ncomms12751.The densities of latex spheres and biological cells can be reliably determined from their sedimentation rate in an albumin gradient under unit gravitational force. PKA inhibits WNT signalling in adrenal cortex zonation and prevents malignant tumour development.ĭrelon C, Berthon A, Sahut-Barnola I, Mathieu M, Dumontet T, Rodriguez S, Batisse-Lignier M, Tabbal H, Tauveron I, Lefrançois-Martinez AM, Pointud JC, Gomez-Sanchez CE, Vainio S, Shan J, Sacco S, Schedl A, Stratakis CA, Martinez A, Val P. This work has been highlighted on the CNRS website (in French) These data on mouse models have further been confirmed in patients with adrenocortical cancer by analysis of gene expression data from the cancer genome atlas consortium. Indeed, when PKA pathway activity is reduced in transgenic mice, WNT pathway activation results in rapid development of aggressive adrenal tumours. Elaborating on their observations on adrenal differentiation, the researchers have shown that PKA also blocks WNT signalling in the context of tumourigenesis. The team had previously shown that abnormal WNT pathway activation resulted in development of benign and malignant tumours of the adrenal cortex, both in mouse models and in patients. This locks cells in fasciculata identity. As cells move away from the source of WNT4 ligand along migration, they become capable of responding to PKA signalling which then blocks WNT pathway activation. This activation inhibits PKA signalling pathway, which locks cells in glomerulosa identity. Activation of WNT signalling relies on WNT4, a diffusible ligand expressed in the outer cortex.

Using combinations of genetically engineered mice, GReD researchers demonstrated that establishment and maintenance of the two functional zones relied on two distinct cell signalling pathways: WNT/b-catenin pathway, which is activated in zona glomerulosa and protein kinase A (PKA), activated in zona fasciculata. This observation suggests that cells receive positional cues instructing their differentiation as glomerulosa or fasciculata as a function of their localisation within the tissue. Despite this continuous flow of cells, the boundary between the two zones and tissue organisation are stable. They further move inside the cortex and change identity to become zona facsiculata cells. After division, cells residing in the periphery of the gland migrate inwards and initially differentiate as glomerulosa cells. The internal zone, or zona fasciculata is organised in cellular cords, responsible for the production of cortisol.Īdrenal cortex cells are constantly renewed throughout life. The external zone or zona glomerulosa is characterised by cell organisation as rosettes, in charge of aldosterone production. Normal adrenal cortex endocrine activity relies on coordinated development of the gland, which is characterised by establishment of distinct concentric cellular zones. At the other end of the spectrum, increased corticosteroid production is associated with profound metabolic disruption (obesity and muscle loss) and severe hypertension. Lack of adrenal steroid production is a life-threatening condition. The periphery is composed of the adrenal cortex, involved in the production of corticosteroids such as cortisol (natural equivalent to cortisone, which is one of the most frequent anti-inflammatory prescription) and aldosterone. The centre of the gland is occupied by adrenal medulla, which synthesizes adrenalin. They constitute the main stress response organ and are composed of two distinct tissues. Adrenal glands are endocrine tissues situated above each kidney.

Zona glomerulosa