The molecular basis for developmental disorders of the pituitary gland in man

The development of the anterior pituitary gland is dependent upon a cascade of signalling molecules and developmental genes that function as transcription factors. Many of these genes are homeobox genes which contain a DNA-binding region or homeobox. Animal models have given a valuable insight into human pituitary disease. For example, Pit-1 and Prop1 mutants are known to have deficiencies of growth hormone, prolactin and thyroid-stimulating hormone. Human phenotypes arising as a result of mutations in these genes are similar to the mouse mutants. Mutations in the novel homeobox gene Hesx1/HESX1 are associated with the highly variable phenotype of septo-optic dysplasia in mouse and man. The unravelling of this complex developmental cascade is just commencing.