Combined pituirary hormone deficency: role of Pit-1 and Prop-1

• Published in: Acta Paediatrica Vol. 88; no. s433; pp. 33 - 41
• Main Authors: Pfaffle, RW, Blankenstin, O, Wüller, S, Kentrup, H
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.12.1999
• Subjects: Combined pitutiary hormone deficiency. growth hormone; hypogonadism; hypothyroidism; mutation; Pit-1; Prop-1
• ISSN: 0803-5253; 1651-2227
• DOI: 10.1111/j.1651-2227.1999.tb14401.x

During fetal development of the anterior pituitary gland, a number of sequential processes occur that effect cell differentiation and proliferation. Molecular anlyses have revealed several steps thay are required for pituitry 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 ofthePITIgene 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 PROPl mutations show combined pituitary hormone deficiency. These patients exhibiy secondary hypogonadism in addition to the deficiencies of Gh, PRL and thyroid‐stimulating hormone (TSH) also seen in patients with PITI mutations. Although all are in the subnormal range, the levels of GH, PRL and TSH in patients with PROP 1mutations are on average, slightly higher than in patients with PITI mulations. Some degree of hypocortisolism may necessitate cortisol substitution in patients with PROP1 mutations.