O-GlcNAcylation is essential for rapid Pomc expression and cell proliferation in corticotropic tumor cells

In this study, we demonstrate that O-GlcNAcylation enzymes were upregulated, particularly in aggressive ACTH-secreting tumors, suggesting a role for O-GlcNAcylation in pituitary adenoma etiology. In addition to the demonstration that O-GlcNAcylation was essential for their proliferation, we show that the endocrine function of pituitary adenoma is also dependent on O-GlcNAcylation. In corticotropic tumors, hyper-secretion of the proopiomelanocortin (POMC)-derived hormone ACTH leads to Cushing's disease, materialized by severe endocrine disruption and increased mortality. We demonstrate that Pomc mRNA is stabilized in an O-GlcNAc-dependent manner in response to corticotrophin-releasing hormone (CRH). By impacting Pomc mRNA splicing and stability, O-GlcNAcylation contributes to this new mechanism of fast hormonal response in corticotropes. Thus, this study stresses the essential role of O-GlcNAcylation in ACTH-secreting adenomas' pathophysiology, including cellular proliferation and hypersecretion.PMID:34418053 | DOI:10.1210/endocr/bqab178
Source: Endocrinology - Category: Endocrinology Authors: Source Type: research