Heritable Disorders of Pituitary Development

J Clin Endocrinol Metab. 1999 Dec;84(12):4362-70. doi: 10.1210/jcem.84.12.6209.


Basic and translational research achievements over the past 2 decades have disclosed the molecular mechanisms underlying several genetic forms of hypopituitarism. Disorders that are limited to the hypothalamic, pituitary, GH axis are caused by mutations in individual components of that axis. Disorders involving GH and one or more additional pituitary hormones are caused by mutations in the homeodomain transcription factors that direct embryological development of the anterior pituitary gland. Pit-1 has a POU-specific and a POU-homeo DNA-binding domain. The phenotype produced by mutations in the PIT1 gene involves deficiencies of GH, PRL, and TSH. Pituitary glands are either small or normally sized. The PROP1 gene encodes a transcription factor with a single paired-like DNA-binding domain. Persons with inactivating mutations in PROP1 have deficiencies of LH and FSH, as well as GH, PRL, and TSH. Their pituitary glands may be small, normally sized, or extremely large and show suprasellar extension. Pituitary degeneration may produce acquired deficiency of ACTH. Expression of the HESX1 gene precedes expression of PROP1 and PIT1, and it is much more widespread. The protein has a paired-like domain, and it competes with the product of PROP1 for DNA-binding. Homozygosity for inactivating mutations of HESX1 produces a complex phenotype that resembles septo-optic dysplasia. Much more needs to be learned about the role of HESX1 mutations in other forms of hypopituitarism.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Basic Helix-Loop-Helix Transcription Factors
  • Carrier Proteins / genetics
  • Homeodomain Proteins / genetics
  • Humans
  • Hypopituitarism / genetics*
  • Membrane Proteins*
  • Mutation
  • Phospholipid Transfer Proteins
  • Pituitary Gland / growth & development*
  • Transcription Factor HES-1
  • Transcription Factors / genetics


  • Basic Helix-Loop-Helix Transcription Factors
  • Carrier Proteins
  • HESX1 protein, human
  • Homeodomain Proteins
  • Membrane Proteins
  • Phospholipid Transfer Proteins
  • Prophet of Pit-1 protein
  • Transcription Factor HES-1
  • Transcription Factors
  • HES1 protein, human