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The Molecular Basis of Hypopituitarism

Authors
  • Radovick, Sally
  • Cohen, Laurie E.
  • Wondisford, Fredric E.
Type
Published Article
Journal
Hormone Research in Paediatrics
Publisher
S. Karger AG
Publication Date
Mar 01, 1998
Volume
49
Issue
1
Pages
30–36
Identifiers
DOI: 10.1159/000053065
Source
Karger
Keywords
License
Green
External links

Abstract

Pit-1 is a pituitary-specific transcription factor responsible for pituitary development and hormone expression in mammals. My laboratory and others have recently described several patients with combined pituitary hormone deficiency (CPHD) due to point mutations in the pit-1 gene. In addition to pit-1, other nuclear factors appear to be necessary for full expression of pituitary genes. A zinc finger transcription factor, Zn-15, is responsible with pit-1 for synergistic activation of the GH gene. The Prl gene is regulated synergistically by pit-1 and the estrogen receptor. Finally, the pit-1 gene itself is regulated by an enhancer element located >10 kb upstream of the transcriptional start. This element contains several pit-1 DNA binding sites and retinoic acid response elements (RAREs). On one of these elements, pit-1 and RAR interact functionally to mediate a synergistic response to RA. Recent data from our laboratory suggests that RA induction of the pit-1 gene can be impaired by pit-1 gene mutations. Study of pit-1 mutations and their diverse pathophysiological mechanisms should increase our understanding of anterior pituitary gland development and gene regulation in normal and disease states.

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