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Michael Greenwood
Molecular Neuroendocrinology Research Group, Bristol Medical School: Translational Health Sciences, University of Bristol, Bristol, United Kingdom
The magnocellular neurones (MCNs) in the hypothalamus make the peptide hormones arginine vasopressin (AVP) and oxytocin (OXT) and release them peripherally into the blood circulation from nerve terminals in the posterior lobe of the pituitary gland (PP), and centrally from dendrites and axon collaterals. Once secreted, these peptides modulate physiological parameters such as blood osmolality, blood pressure and blood glucose by acting on specific receptors to maintain homeostasis. There is a resurgence in interest in mechanisms regulating AVP and OXT release, which stems from clinical associations with body mass index, and consequently diabetes, obesity, and metabolic syndrome. When we eat a meal the gut releases hormones, aptly grouped as gut peptides, to control the amount of food and fluid we ingest by acting on specific receptors to promote a feeling of fullness. Interestingly, MCNs express receptors for gut peptides GLP-1, GIP and CCK at nerve terminals in the PP, and I will present our data on how those receptors integrate signals from circulating gut peptides.
Svenja Leibnitz, Mirjam Christ-Crain
Department of Endocrinology, University Hospital Basel, Switzerland
Department of Clinical Research, University Hospital Basel, Switzerland
Oxytocin deficiency is emerging as a potential pituitary disorder in patients with vasopressin deficiency, currently known as central diabetes insipidus. Vasopressin is vital for renal water reabsorption, and its inadequate secretion leads to polyuria and polydipsia. However, despite adequate treatment, patients often experience residual psychological symptoms, such as heightened anxiety and alexithymia, reduced empathy, and impaired social interaction. Both vasopressin (AVP) and oxytocin, nine-amino acid neuropeptides, are released from axon terminals projecting to the posterior pituitary. Disruption of the hypothalamic-pituitary axis leading to AVP deficiency can also impact the oxytocin system, which is crucial for regulating socio-emotional functions such as attachment, fear extinction, emotion recognition, and empathy. Given this evidence, psychopathological manifestations in AVP-deficient patients could be due to a concomitant oxytocin deficiency. Since measuring oxytocin at baseline and during standard pituitary provocation tests is not useful, we recently investigated MDMA as a stimulation test and found a significantly lower increase in oxytocin and the absence of oxytocin-induced effects compared to healthy controls. Our ongoing randomized, placebo-controlled, double-blind study is investigating the potential benefits of intranasal oxytocin in AVP deficiency. Our results could lead to a new therapeutic approach improving psychological symptoms and socio-emotional functioning of patients with vasopressin deficiency.
Julian Zacharjasz1,Ewelina Kałużna1, Marta Sztachera1 and Monika Piwecka1
Department of Non-coding RNAs, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Poznan, Poland
Non-coding RNAs (ncRNAs) are RNA molecules that are not translated into proteins, however they play vital role in the regulation of gene expression driving cell fate and stimuli response. How non-coding RNAs such as long non-coding RNAs (lncRNAs), circular RNAs (circRNAs) or microRNAs (miRNAs) are involved in regulation of gene expression programs in different cell types within the pituitary gland still lack comprehensive understanding. We hypothesize that cell-type specific ncRNA are essential contributors to gene expression regulation in the pituitary in different stages of development. We investigated ncRNA expression patterns in mouse pituitary and identified >4000 lncRNAs and >400 circular RNAs in adult pituitary. Additionally, we identified miRNAs that are dynamically regulated over postnatal pituitary development (neonatal, around puberty and adult) and created a resource of stage-specific miRNAs. We evaluate the spatial expression pattern of selected ncRNAs using RNA in situ hybridization methods and spatial transcriptomics.
Funding: NCN, Opus (2021-2024) – project „Non-coding RNAs at single-cell resolution in the pituitary gland and their role in the regulation of gene expression”
Konopińska N., Słocińska M., Urbański A.
Department of Animal Physiology and Developmental Biology, Adam Mickiewicz University, Poznań, Poland
Invertebrates and vertebrates have a significant number of physiological similarities. Neuropeptides, which are synthesized and secreted by the neuroendocrine system, are known to play a crucial role for both. One of the largest families of neuropeptides found throughout the animal kingdom are tachykinins (TKs). In insects, neuropeptides showing structural similarity to TKs are tachykinin-related peptides (TRPs). They are involved in neuronal depolarization, processing of chemosensory information and nociception. Interestingly, there is strong functional and structural homology between substance P (SP, one the of mammalian TKs) and insect TRPs, e.g., both neuropeptides have anti-apoptotic properties. Also, our latest results revealed many similarities between immunomodulatory action of these neuropeptides. Moreover, SP can activate insect TRP receptor.
Our comparative research can be successfully used in the search for new models to study hormonal regulation of many processes occurring in humans. They will also enrich knowledge about neuroendocrinology, immunology, and entomology.
Funding: OPUS 2021/41/B/NZ9/01054
Naveen Nedunchezhian1, Savani Anbalagan1,2
1Institute of Molecular Biology and Biotechnology, Faculty of Biology, Adam Mickiewicz University in Poznań, Poznań, Poland
2Weizmann Institute of Science, Department of Molecular Cell Biology, Rehovot, Israel
Neurohypophysis (posterior pituitary) is a major neuroendocrine interface in the brain through which water homeostasis is maintained. Neurohypophysis majorly consists of glial pituicytes, neuropeptides oxytocin- and vasopressin- loaded synapses and permeable capillaries. We recently identified that pituicyte-derived secreted factors can regulate neurohypophyseal neurovascular morphogenesis. However, the role of other secreted factors expressed in the neurohypophysis in the neurovascular morphogenesis is unknown. Towards this goal, we have been employing pharmacological and genetic perturbations to explore the roles of candidate molecules that could regulate neurohypophyseal synapse morphogenesis. Our studies of the glial pituicytes are expected to reveal novel players in the development of a key neuroendocrine interface conserved in vertebrates.
Funding: NCN SONATA BIS (2020/38/E/NZ3/00090)
