title: Distinct proteomic profiles in post-mortem pituitary glands from bipolar disorder and major depressive disorder patients.
abstract: Disturbances of the hypothalamic-pituitary-adrenal axis have been implicated in the pathophysiology of bipolar disorder (BD) and major depressive disorder (MDD). To examine this further, we carried out proteomic profiling of post-mortem pituitaries from 13 BD and 14 MDD patients, in comparison to 15 controls. Liquid chromatography-mass spectrometry (LC-MS(E)) analysis showed that BD patients had significantly increased levels of the major pituitary hormones pro-opiomelanocortin (POMC) and galanin. BD patients also showed changes in proteins associated with gene transcription, stress response, lipid metabolism and growth signalling. In contrast, LC-MS(E) profiling revealed that MDD patients had significantly decreased levels of the prohormone-converting enzyme carboxypeptidease E and follow-up enzymatic analysis showed decreased activity of prolyl-oligopeptidase convertase. This suggested that altered prohormone processing may occur in pituitaries of MDD patients. In addition, MDD patients had significant changes in proteins involved in intracellular transport and cytoskeletal signalling. Finally, we carried out selective reaction monitoring (SRM) mass spectrometry profiling for validation of protein changes in key biological pathways. This confirmed increased POMC levels in BD patients with no change in the levels of this prohormone in MDD. This study demonstrates that proteomic profiling analysis of the pituitary can lead to new insights into the pathophysiology of BD and MDD. Also, given that the pituitary directly releases a variety of bioactive molecules into the bloodstream, many of the proteins identified here could serve as focal points in the search for peripheral biomarkers in clinical or drug treatment studies of BD and MDD patients.
authors.affiliation: Department of Chemical Engineering and Biotechnology, University of Cambridge, Tennis Court Road, Cambridge CB21QT, UK. Electronic address: vs308@cam.ac.uk.
authors.forename: Viktoria
authors.initials: V
authors.lastname: Stelzhammer
authors.affiliation: Department of Chemical Engineering and Biotechnology, University of Cambridge, Tennis Court Road, Cambridge CB21QT, UK. Electronic address: ma471@cam.ac.uk.
authors.forename: Murtada
authors.initials: M
authors.lastname: Alsaif
authors.affiliation: Department of Chemical Engineering and Biotechnology, University of Cambridge, Tennis Court Road, Cambridge CB21QT, UK. Electronic address: mkc31@cam.ac.uk.
authors.forename: Man K
authors.initials: MK
authors.lastname: Chan
authors.affiliation: Department of Chemical Engineering and Biotechnology, University of Cambridge, Tennis Court Road, Cambridge CB21QT, UK. Electronic address: hr288@cam.ac.uk.
authors.forename: Hassan
authors.initials: H
authors.lastname: Rahmoune
authors.affiliation: Department of Chemical Engineering and Biotechnology, University of Cambridge, Tennis Court Road, Cambridge CB21QT, UK. Electronic address: hs463@cam.ac.uk.
authors.forename: Hannah
authors.initials: H
authors.lastname: Steeb
authors.affiliation: Department of Chemical Engineering and Biotechnology, University of Cambridge, Tennis Court Road, Cambridge CB21QT, UK. Electronic address: pg110@cam.ac.uk.
authors.forename: Paul C
authors.initials: PC
authors.lastname: Guest
authors.affiliation: Department of Chemical Engineering and Biotechnology, University of Cambridge, Tennis Court Road, Cambridge CB21QT, UK; Department of Neuroscience, Erasmus MC, NL-3015 GE Rotterdam, The Netherlands. Electronic address: sb209@cam.ac.uk.
authors.forename: Sabine
authors.initials: S
authors.lastname: Bahn
mesh_terms: D000328:Adult; D001344:Autopsy; D001714:Bipolar Disorder / Q000378:metabolism*; D002853:Chromatography, Liquid; D003865:Major Depressive Disorder / Q000378:metabolism*; D005260:Female; D019004:Galanin / Q000378:metabolism*; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D010902:Pituitary Gland / Q000378:metabolism*; D011333:Pro-Opiomelanocortin / Q000378:metabolism*; D040901:Proteomics
chemical_list: D011333:Pro-Opiomelanocortin; D019004:Galanin
keywords: Bipolar disorder; HPA-axis; Major depressive disorder; Mass spectrometry; Pituitary