570 Biowissenschaften; Biologie
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Schlagworte
- 5' UTR (1)
- Fluoreszenzmikroskopie (1)
- Genexpression (1)
- Glucocorticosteroidrezeptor (1)
- HPA axis (1)
- Hydrocortison (1)
- Lymphozyt (1)
- Psychobiologie (1)
- Pulsatilität (1)
- Stress (1)
- Stressreaktion (1)
- Transkription <Genetik> (1)
- cortisol (1)
- immunity (1)
- lymphocytes (1)
- membrane glucocorticoid receptor (1)
- membraner Glucocorticoidrezeptor (1)
- post-transcriptional regulation (1)
- post-transkriptionelle Regulierung (1)
- pulsatility (1)
Institut
- Psychologie (2) (entfernen)
In this thesis, in order to shed light on the biological function of the membrane-bound Glucocorticoid Receptor (mGR), proteomic changes induced by 15 min in vivo acute stress and by short in vitro activation of the mGR were analyzed in T-lymphocytes. The numerous overlaps between the two datasets suggest that the mGR mediates physiologically relevant actions and participates in the early stress response, triggering rapid early priming events that pave the way for the slower genomic GC activities. In addition, a new commercially available method with suitable sensitivity to detect the human mGR is reported and the transcriptional origin of this protein investigated. Our results indicates that specific GR-transcripts, containing exon 1C and 1D, are associated with the expression of this membrane isoform.
Cortisol exhibits typical ultradian and circadian rhythm and disturbances in its secretory pattern have been described in stress-related pathology. The aim of this thesis was to dissect the underlying structure of cortisol pulsatility and to develop tools to investigate the effects of this pulsatility on immune cell trafficking and the responsiveness of the neuroendocrine system and GR target genes to stress. Deconvolution modeling was set up as a tool for investigation of the pulsatile secretion underlying the ultradian cortisol rhythm. This further allowed us to investigate the role of the single cortisol pulses on the immune cell trafficking and the role of induced cortisol pulses on the kinetics of expression of GR target genes. The development of these three tools, would allow to induce and investigate in future the significance of single cortisol pulses for health and disease.