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HPA-aksen og depression - Fra konceptuel model til matematisk modellering af processer i styringen af niveauet af cortisol
Integreret speciale - modelbyggervariant, 2. modul, Vinter 2012, id:444
Vejleder:Johnny Ottesen
Findes på RUb: Ja
Abstract
English abstract
Altered levels of the steroid hormone cortisol has been observed in some melancholic depressed patients. The reason for this is not fully understood. The level of cortisol in the blood is regulated by the neuroendocrine system called the hypothalamic-pituitary-adrenal(HPA)-axis. By proposing mathematical models for cortisol's synthesis and transport in the blood parts of this system are being investigated. For the ACTH-induced cortisolsynthesis is established a comprehensive mechanism-based model. This model can be parted into submodels to investigate specific parts of the cortisolsynthesis. MatLab simulations of a sub-model of the activation of protein kinase A (PKA) indicates the occurrence of a maximum activation of PKA, at the total concentration of cyclic adenosine monophosphate being four times the total concentration of the PKA tetrameric. Simulations of a sub-model for the system from the concentration of cytosolic cholesterol (CC) to the secretion of cortisol shows that the concentration of cholesterol in the mitochondrial inner membrane and the synthesis of steroids is strongly influenced by the concentration of the cholesterol transport protein StAR and the degree of phosphorylation. Variations of CC are of importance only at concentrations being less than 1000 nM, which is half of the standard concentration estimated in the literature. Furthermore are set up models of activation of melanocortin 2 receptor and cortisol mobilization in the cell cytostol on the basis of the curent knowledge. Simulations of these models, however do not yet show operational results. The model developed in this project for cortisol transport in the blood describes the binding of the hormone to the carrier protein, corticosteroid binding globulin (CBG). Simulations of the model shows that CBG increases the total concentration of cortisol in the blood, while the concentration of cortisol on the free form remains the same. The output of the concentration of free cortisol, however, is at a high level compared with the literature. Changes in the rates of production and of elimination can approximate this picture, but maybe the reason for the high concentrations are to be found in the model's simplified construction, which as an example does not include an exchange of cortisol in the body's tissues.

Database opslag den: 18-03-2019