Endocrine Abstracts

The immune microenvironment plays a central but ambivalent role in tumourigenesis. During initial phases of neoplasia, both innate and adaptive immune cells recognize and destroy tumour cells. However, during the process of immunoediting, tumour cells progressively reshape the microenvironment and use immune cells to favour neoangiogenesis, tumour growth and metastasis. Until recently, the role of immune response in the pathogenesis of ACC had remained elusive. Analysis of the...

The adrenal cortex arises from the adrenogonadal primordium, which is also involved in the formation of the gonadal anlagen and is characterized by expression of the nuclear receptor Sf1. After individualisation, the adrenal primordium undergoes a series of developmental events that culminate with establishment of functional zonation, characterised by differentiation of zona glomerulosa and zona fasciculata. In the past 7 years, we have developed a number of mouse models recap...

Maturation of the definitive adrenal cortex occurs between 3 and 6 weeks post-partum and involves onset of CYP11B2 expression and establishment of the laminin-encased 3D structure of glomeruli that contain rosettes of 10 to 15 zona glomerulosa (zG) cells that work in coordination to produce optimal amounts of aldosterone. Although this process is dependent on canonical WNT/b-catenin signaling, cellular sources of WNT ligands remain elusive and the mechanisms involved in the ex...

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...