Figure 4

Experimental and simulated ACTH concentration profiles. The figure shows experimental ACTH profiles (black and blue lines) from murine AtT-20 pituitary cell lines described in[44] and simulations (green and red lines) after data fitting with different HPA network models. A) The black line corresponds to an experiment in which the system was exposed to 10 nM of CRH at time zero, the blue line corresponds to an experiment in which - in addition to 10 nM - 100 nM of cortisol was administered at time zero. The error bars show the 95% confidence intervals for the measurements at the different time points. B) Fit of experimental data with the HPA network model of Figure2. C) Fit of experimental data with the HPA network model of Figure2 after knockout of the membrane glucocorticoid receptor GPCR pathway. D) Fit of experimental data with the HPA network model of Figure1. The results underpin the need for including the membrane glucocorticoid receptor GPCR in models of the pituitary gland cells.