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Long-term, Dynamic Remodelling of the Corticotroph Transcriptome and Excitability After a Period of Chronic Stress.
Endocrinology
October 2024
Centre for Discovery Brain Science, Edinburgh Medical School: Biomedical Sciences, University of Edinburgh, Edinburgh EH8 9AG, UK.
Chronic stress results in long-term dynamic changes at multiple levels of the hypothalamic-pituitary-adrenal (HPA) axis resulting in stress axis dysregulation with long-term impacts on human and animal health. However, the underlying mechanisms and dynamics of altered of HPA axis function, in particular at the level of pituitary corticotrophs, during a period of chronic stress and in the weeks after its cessation (defined as "recovery") are very poorly understood. Here, we address the fundamental question of how a period of chronic stress results in altered anterior pituitary corticotroph function and whether this persists in recovery, as well as the transcriptomic changes underlying this.
View Article and Find Full Text PDFStructural Basis for Antagonist Binding to Vasopressin V1b Receptor Revealed by the Molecular Dynamics Simulations.
Biopolymers
January 2025
Faculty of Chemistry, University of Gdańsk, Gdańsk, Poland.
Article Synopsis
- - The V1b receptor (V1bR), located in the anterior pituitary, regulates the HPA axis by prompting the release of ACTH, which ultimately stimulates cortisol production; dysfunction in this axis is linked to psychiatric disorders.
- - Inhibiting the V1b receptor could help treat stress-related conditions like anxiety and depression, with the selective antagonist nelivaptan being a key focus of research for its effects on this receptor.
- - This study involved extensive molecular dynamics simulations of the V1bR-nelivaptan complex to better understand how the antagonist binds to the receptor, identifying specific residues that contribute to selective binding, which aligns with known structures of similar receptors.
PACS-1 Interacts with TRPC3 and ESyt1 to Mediate Protein Trafficking while Promoting SOCE and Cooperatively Regulating Hormone Secretion.
ACS Omega
August 2024
Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, ON N6A 5C1, Canada.
Corticotropic cells of the anterior pituitary gland release adrenocorticotropic hormone (ACTH) in a regulated manner to promote the production of cortisol and androgens. The process of ACTH secretion is partly mediated by the phosphofurin acidic cluster sorting protein 1 (PACS-1); however, the underlying mechanisms behind this regulation remain unclear. Herein, we demonstrated PACS-1 interactions with the short transient receptor potential channel 3 (TRPC3) calcium transporter and the extended synaptotagmin-1 (ESyt1) endoplasmic reticulum-plasma membrane tethering protein.
View Article and Find Full Text PDFEndobiogenic Biology of Function Indices in a Cohort of Kidney Transplant Recipients.
Medicina (Kaunas)
June 2024
Gastroenterology, Nephrourology and Surgery Clinic, Faculty of Medicine, Vilnius University, LT03101 Vilnius, Lithuania.
: Endobiogeny is a global systems approach to human biology based on the concept that the endocrine system manages the metabolism. Biology of function (BoF) indices are diagnostic tools in endobiogenic medicine that reflect the action of the endocrine system on the cells and the metabolic activity of an organism. Kidney transplant recipients are a very specific patient population due to their constant use of immunosuppressive agents such as steroids and anamnesis of chronic kidney disease.
View Article and Find Full Text PDFConversion of spikers to bursters in pituitary cell networks: Is it better to disperse for maximum exposure or circle the wagons?
PLoS Comput Biol
January 2024
Department of Mathematics, Florida State University, Tallahassee, Florida, United States of America.
The endocrine cells of the pituitary gland are electrically active, and in vivo they form small networks where the bidirectional cell-cell coupling is through gap junctions. Numerous studies of dispersed pituitary cells have shown that typical behaviors are tonic spiking and bursting, the latter being more effective at evoking secretion. In this article, we use mathematical modeling to examine the dynamics of small networks of spiking and bursting pituitary cells.
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