Endocrine Abstracts

Dysfunction in the mechanisms that regulate cell numbers in the pituitary gland can underlie hypopituitarism as well as the generation of tumours. Investigations into how these conditions arise has led to an interest in identifying mechanisms for correct maintenance of endocrine cells throughout life. Currently, the source and identity of signals promoting this maintenance in the postnatal pituitary are not known. We have previously shown that pituitary-specific disruptions in...

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Cushing’s disease is caused by corticotroph adenomas of the pituitary. To explore molecular mechanisms of endocrine autonomy, we recently performed exome sequencing of 10 corticotroph adenomas1 identifying somatic mutations in the USP8 deubiquitinase gene in 4 of 10 adenomas. The mutations clustered in the 14-3-3 protein binding motif enhancing proteolytic cleavage and catalytic activity of USP8. Cleaved USP8 led to increased EGF receptor deubiquitination impai...