Endocrine Abstracts

The cAMP signaling pathway plays an important role in cell proliferation and differentiation, and can be altered at multiple levels in endocrine tumors. Its central component is the protein kinase A (PKA). Inactivating mutations of PRKAR1A are observed in CNC (a dominant autosomal hereditary disease responsible for primary pigmented nodular adrenocortical disease, cardiac myxoma and lentiginosis). Most PRKAR1A mutations lead to mRNA unstability and protein degrad...

In adult mice the adrenal cortex is divided, in two distinct functional zones, outermost zona glomerulosa (ZG) and innermost zona fasciculata (ZF), encapsulated by a thin layer of mesenchymal cells (capsule). The adrenal cortex undergoes constant centripetal cell renewal, reliying on recruitment of progenitors located within an outer cortex niche. Progenitors initially differentiate as ZG cells and undergo lineage conversion to ZF as they move within the cortex. This relies on...

The adrenal gland produces corticosteroids essential for hydromineral and metabolic homeostasis. It is organised, in mice, in two concentric layers. The zona glomerulosa (zG) and fasciculate (zF), renewed from progenitors located in the capsular periphery. Centripetal renewal and maintenance of cortical zonation are dependant of a balance between WNT/β-catenin and ACTH/PKA signalling pathways. They provide recruitment and consecutive differentiation of progenitors into zG...

Adrenocortical carcinoma (ACC) is an infrequent and aggressive cancer that originates from steroidogenic cells within the adrenal cortex. Half of patients present with metastatic spread at initial diagnosis, and to date, there is no curative therapy for advanced disease. Recent genomic analysis has established that the most aggressive subgroup of ACC patients have overlapping alterations in the WNT/B-catenin pathway and the p53/RB pathway. We therefore set out to develop a met...

Adrenocortical carcinoma (ACC) is a rare and aggressive cancer that originates from steroidogenic cells within the adrenal cortex. The most common alteration in ACC patients is inactivation of the transmembrane E3 ubiquitin-ligase Zinc and Ring Finger 3 (ZNRF3), which is responsible for inhibiting the canonical WNT/Beta-catenin pathway. Using Cre/loxP strategy, we showed that inactivation of Znrf3 in the adrenal cortex resulted in an initial hyperplasia by 6-weeks, af...