Combined pituitary hormone deficiency: role of Pit-1 and Prop-1.
During fetal development of the anterior pituitary gland, a number of sequential processes occur that affect cell differentiation and proliferation. Molecular analyses have revealed several steps that are required for pituitary cell line specification and have identified specific factors that control these steps. The gene encoding the pituitary transcription factor 1 (Pit-1) is expressed during differentiation steps that take place quite late in the development of the anterior pituitary gland. Clinically, patients with mutations of the PIT1 gene are characterized by severe deficiencies in growth hormone (GH) and prolactin (PRL), and often develop secondary hypothyroidism. A second pituitary transcription factor is known as Prophet of Pit-1 (Prop-1), and a mutation of the Prop1 gene has been detected in Ames dwarf mice. Several Prop1 mutations have been identified that structurally affect the 'paired-like' DNA-binding domain of the Prop-1 protein molecule. Patients with PROP1 mutations show combined pituitary hormone deficiency. These patients exhibit secondary hypogonadism in addition to the deficiencies of GH, PRL and thyroid-stimulating hormone (TSH) also seen in patients with PIT1 mutations. Although all are in the subnormal range, the levels of GH, PRL and TSH in patients with PROP1 mutations are, on average, slightly higher than in patients with PIT1 mutations. Some degree of hypocortisolism may necessitate cortisol substitution in patients with PROP1 mutations.
Pfäffle
R W
RW
Department of Pediatrics, RWTH Aachen School of Medicine, Germany. rpfaeffle@post.klinikum.rwthaachen.de
Blankenstein
O
O
Wüller
S
S
Kentrup
H
H
D000818:Animals; D001120:Arginine / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D051379:Mice; D009154:Mutation; D010641:Phenotype; D010907:Pituitary Hormones / Q000172:deficiency*; D050817:Transcription Factor Pit-1; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic; D014364:Tryptophan / Q000235:genetics
D001120:Arginine; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D010907:Pituitary Hormones; D050817:Transcription Factor Pit-1; D014157:Transcription Factors; D014364:Tryptophan; C494187:POU1F1 protein, human; C494185:Pou1f1 protein, mouse; C102134:Prophet of Pit-1 protein