Pituitary deficiency and regeneration: in search of underlying mechanisms and therapeutic targets.

The pituitary is the ‘master gland’ producing hormones that control vital physiological processes like growth, metabolism, reproduction and stress response. Obviously, defects in pituitary function (hypopituitarism) cause severe and life-threatening health problems. Hypopituitarism is treated with lifelong hormone replacement. However, patients taking these hormones suffer from serious side effects. Moreover, administration of hormones cannot mimic the gland’s dynamic secretion pattern. Therefore, it would be superior to restore the defective pituitary tissue and function. In the present project, we take 2 approaches. First, we will search for mechanisms that drive the pituitary’s capacity to repair damage. Recently, we designed a pituitary injury (mouse) model and discovered that the gland can restore destroyed cells, a property unknown before. Unraveling the mechanisms of regeneration will identify regulatory pathways that can be targeted for restoration. Second, we will search for mechanisms that underlie genetic forms of hypopituitarism. So far, most studies were done in mice but it is unknown whether principles also apply to humans. We will set up a ‘pituitary-in-a-dish’ model starting from human pluripotent stem cells, in which pituitary development, function and disease will be explored. Unraveling cause and mechanisms of (human) hypopituitarism will open the way to novel, more targeted and less burdening therapies, thereby embracing the field of regenerative medicine.