Defective retinoic acid regulation of the Pit-1 gene enhancer: a novel mechanism of combined pituitary hormone deficiency

Mol Endocrinol. 1999 Mar;13(3):476-84. doi: 10.1210/mend.13.3.0251.

Abstract

Pit-1 is a pituitary-specific transcription factor responsible for pituitary development and hormone expression in mammals. Pit-1 contains two protein domains, termed POU-specific and POU-homeo, which are both necessary for DNA binding and activation of the GH and PRL genes and regulation of the PRL, TSH-beta subunit (TSH-beta), and Pit-1 genes. Pit-1 is also necessary for retinoic acid induction of its own gene during development through a Pit-1-dependent enhancer. Combined pituitary hormone deficiency is caused by defective transactivation of target genes in the anterior pituitary. In the present report, we provide in vivo evidence that retinoic acid induction of the Pit-1 gene can be impaired by a Pit-1 gene mutation, suggesting a new molecular mechanism for combined pituitary hormone deficiency in man.

Publication types

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

MeSH terms

  • Animals
  • Child, Preschool
  • DNA / metabolism
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Enhancer Elements, Genetic
  • Gene Expression Regulation
  • Human Growth Hormone / genetics
  • Human Growth Hormone / metabolism
  • Humans
  • Hypothyroidism / metabolism
  • Male
  • Mutation*
  • Pituitary Hormones / deficiency*
  • Prolactin / genetics
  • Prolactin / metabolism
  • RNA, Messenger
  • Receptors, Retinoic Acid / metabolism
  • Retinoic Acid Receptor alpha
  • Signal Transduction
  • Transcription Factor Pit-1
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Tretinoin / metabolism*

Substances

  • DNA-Binding Proteins
  • POU1F1 protein, human
  • Pituitary Hormones
  • RARA protein, human
  • RNA, Messenger
  • Receptors, Retinoic Acid
  • Retinoic Acid Receptor alpha
  • Transcription Factor Pit-1
  • Transcription Factors
  • Human Growth Hormone
  • Tretinoin
  • Prolactin
  • DNA