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Trial Lecture – time and place
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Adjudication committee
- First opponent: Professor Marianne Skovsager Andersen, University of Southern Denmark,
- Second opponent: Professor Frédéric Castinetti, Aix Marseille Université, France
- Third member and chair of the evaluation committee: Professor Jørn Vegard Sagen, University of Oslo
Chair of the Defence
Professor Anita Göndör, University of Oslo
Principal Supervisor
Vice-Rector Jens Petter Berg, University of Oslo
Summary
Corticotroph tumors, a subtype of pituitary neuroendocrine tumors (PitNETs). Functioning corticotroph adenomas (FCA) secrete excess biologically active adrenocorticotropic hormone (ACTH), causing Cushing’s disease, whereas silent corticotroph adenomas (SCA) are typically diagnosed as non-functioning pituitary adenomas (NFPAs) and present with mass-related symptoms. Despite their shared lineage, SCA tend to be larger, more aggressive, and more prone to recurrence. Their hormonal silence remains poorly understood, but may involve impaired proopiomelanocortin (POMC) processing, defective secretory pathways, and reduced activity of the prohormone convertase PC1/3 (PCSK1).
This PhD project investigated factors that may contribute to hormonal silence and aggressiveness in corticotroph tumors, focusing on the PC1/3 inhibitor PCSK1N, the cytoskeletal regulator PDZ and LIM domain protein 1 (PDLIM1), and endoplasmic reticulum (ER) stress. We quantified PCSK1N and corticotroph marker expression in patient-derived FCA and SCA samples and assessed associations with clinical features. We induced ER stress in mouse corticotroph tumor cells and primary human FCA cultures to examine its effects on cell survival and ACTH production. Lastly, PDLIM1 was overexpressed in mouse corticotroph tumor cells to assess its effects on cell viability, migration, and morphology related to invasive behavior.
We found that corticotroph cells rely on effective ER function for ACTH production and secretion. ER stress increased PCSK1N expression and reduced secreted ACTH, suggesting a potential mechanism contributing to hormonal silence in SCA. PDLIM1 expression was higher in SCA than in FCA, and its overexpression promoted cell viability and migration in vitro, indicating a possible role in tumor aggressiveness. These findings highlight ER stress, PCSK1N, and PDLIM1 as potential contributors that influence hormonal silence and invasive behavior in corticotroph tumors.
Additional information
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