Integration of an anterior pituitary gland cell model into the HPA network. Diagram of the biochemical feedback network of the HPA axis after incorporation of the cortisol mediated feedback mechanisms in the anterior pituitary gland cells. The recently found membrane glucocorticoid receptor GPCR and the intracellular receptor GR introduced in act on different time scales. The modeling of the corresponding feedback mechanisms requires a distinction between slow genomic processes within the nucleus and fast non-genomic processes within the cytoplasm. In particular, the dimerized cortisol-glucocorticoid receptor complex (GR complex) and the transcription factors TF associated to the CRH receptor CRHR are explicitly considered. See Figure3 for further details.