Basic science and clinical research advances in the pituitary transcription factors: Pit-1 and Prop-1

Abstract

The pituitary-specific transcription factors, Pit-1 (also called Pou1f1) and prophet of Pit-1 (Prop-1), are critical for normal pituitary development and function. The aim of the present review is to highlight the recent basic science and clinical research advances in these transcription factors, as they relate to signaling pathway interactions, gene regulation, and mutations in human diseases. A number of important basic research discoveries have been made in the area of the pituitary-specific transcription factors, Pit-1 and Prop-1. Among these findings include: the effects of the Pit-1 coactivators, GATA-2 and TRAP-220, on the transcriptional regulation of the TSHbeta gene and thyrotropin expression, characterization of a novel pituitary regulator of Pit-1 expression, Atbf1, elucidation of the roles of Wnt and Notch signaling on Prop-1-mediated specification of the Pit-1 cell lineage and gonadotropes, and the identification of regulatory regions of the Prop-1 gene. Advances in clinical research include: the identification of novel mutations in the human POU1F1 and PROP-1 genes, and screening guidelines for patients with combined pituitary hormone deficiencies and possible mutations in these transcription factors. Research into the complex interplay of signaling pathways and transcription factors that regulate the pituitary gland are important areas of developmental biology and normal physiology. Clinically, such research has important implications for human diseases by identifying inheritable transcription factor mutations that may cause pituitary hormonal deficiencies.