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Endocrine Abstracts (2018) 56 S17.1 | DOI: 10.1530/endoabs.56.S17.1

France.


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 recapitulating alterations of WNT/b-catenin and PKA signalling pathways identified in patients presenting with adrenal cortex tumours. This has allowed us to demonstrate that constitutive WNT/b-catenin pathway activation causes the development of both benign aldosterone producing adenomas and to a lesser extent adrenal cortex carcinomas, whereas constitutive PKA signalling is associated with the development of benign glucocorticoid-producing tumours. Beyond tumourigenesis, these experiments have also shed light on the mechanisms involved in adrenal cortex development and in particular functional adrenal cortex zonation. Indeed, we have shown that this process relies on a subtle equilibrium between WNT pathway activation by WNT4/RSPO3 in zona glomerulosa and PKA activation by ACTH/MC2R in zona fasciculata. These data emphasize the idea that adrenal tumourigenesis and differentiation share common regulators and pathways. This is further exemplified by our latest experiments showing that the histone methyltransferase EZH2, which is overexpressed in adrenal cortex carcinomas, is also a key player in regulating steroidogenic cell differentiation and maintaining adrenal identity as opposed to gonadal identity. These observations could be relevant to the observation that PMAH with ARMC5 mutations abnormally express a number of gonadal markers. Altogether these findings demonstrate the need for studies integrating analysis of patients’ data with findings of basic studies on the mechanisms of adrenal development and differentiation.

Volume 56

20th European Congress of Endocrinology

Barcelona, Spain
19 May 2018 - 22 May 2018

European Society of Endocrinology 

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