A diagnosis of inherited combined pituitary deficiency due to a PIT-1 mutation was suspected in view of the short stature with associated multiple pituitary hormone deficiencies.
To determine the basis for this, we performed histological analysis of Pit1- and Prop1-deficient dwarf mouse pituitaries throughout fetal and postnatal development.
Mutations of the pituitary transcription factor gene POU1F1 (the human homologue of mouse Pit1) are responsible for deficiencies of GH, prolactin and thyroid stimulating hormone (TSH) in Snell and Jackson dwarf mice and in man, while the production of adrenocorticotrophic hormone (ACTH), luteinizing hormone (LH) and follicle stimulating hormone (FSH) is preserved.
Using the Pit-1-defective Snell dwarf as a genetic background, we demonstrate that the Pit-1 gene utilizes distinct enhancers for initial gene activation and for subsequent autoregulation (required for maintenance of expression) and that Pit-1-dependent activation of the distal enhancer can be mediated in the absence of the early enhancer.