Figure 3.

The three core feedback pathways of the (anterior) pituitary gland cell model. Illustration of the intracellular pathways of the extended HPA model of Figure 2 showing the three main feedback mechanisms (with respect to the involved receptors) in the anterior pituitary gland cells. A) Genomic pathway of the GR mediated feedback: Outline of the modeled species involved in the inhibition of POMC (Proopiomelanocortin) transcription which corresponds to the inhibition of ACTH production. ACTH is obtained via post-translational cleavaging of the POMC protein. The central transcription factor is the GR-cortisol complex which down regulates the POMC transcription and enhances the production of the GR receptor. B) Non-genomic pathway of the GPCR mediated feedback: The non-genomic negative feedback mechanism via the glucocorticoid membrane receptor GPCR, inhibiting the release of ACTH. C) CRHR mediated feedback: The positive feedback mechanisms associated with the CRH membrane receptor (CRHR), which causes an increased release of ACTH from vesicles and an increased expression of the POMC gene.