Pit-1-dependent expression of the receptor for growth hormone releasing factor mediates pituitary cell growth

Nature. 1992 Dec;360(6406):765-8. doi: 10.1038/360765a0.

Abstract

In Snell (dw) and Jackson (dwJ) dwarf mice, mutations in the gene encoding Pit-1, a tissue-specific POU-domain transcription factor, lead to the absence of somatotroph, lactotroph and thyrotroph cells. Pre-somatotroph proliferation is stimulated by increased intracellular levels of cyclic AMP, normally induced by growth hormone releasing factor (GRF; refs 7-17). Here we report the cloning of mouse and rat complementary DNAs encoding a new member of the seven-transmembrane-helix, G-protein-coupled receptor family restricted to the pituitary gland, which mediates increases in intracellular cAMP and cAMP-dependent gene transcription in response to GRF. The receptor is expressed in a spatial and temporal pattern corresponding precisely to growth hormone gene expression, and neither is expressed in dw/dw mice. The pituitary hypoplasia in these mice thus appears to be due, at least in part, to the absence of GRF receptor, which is in turn due to the absence of functional Pit-1.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cell Division / drug effects
  • Cloning, Molecular
  • Cyclic AMP / metabolism
  • Cyclic AMP / pharmacology
  • DNA / genetics
  • DNA-Binding Proteins / pharmacology*
  • Dwarfism, Pituitary / genetics
  • GTP-Binding Proteins / metabolism
  • Gene Expression / drug effects*
  • Growth Hormone-Releasing Hormone / pharmacology
  • Mice
  • Mice, Mutant Strains
  • Molecular Sequence Data
  • Pituitary Gland / cytology*
  • Pituitary Gland / metabolism
  • RNA, Messenger / genetics
  • Rats
  • Receptors, Neuropeptide*
  • Receptors, Neurotransmitter / chemistry
  • Receptors, Neurotransmitter / genetics*
  • Receptors, Neurotransmitter / physiology
  • Receptors, Pituitary Hormone-Regulating Hormone*
  • Transcription Factor Pit-1
  • Transcription Factors / pharmacology*
  • Transcription, Genetic / drug effects

Substances

  • DNA-Binding Proteins
  • Pit1 protein, mouse
  • Pou1f1 protein, rat
  • RNA, Messenger
  • Receptors, Neuropeptide
  • Receptors, Neurotransmitter
  • Receptors, Pituitary Hormone-Regulating Hormone
  • Transcription Factor Pit-1
  • Transcription Factors
  • DNA
  • Growth Hormone-Releasing Hormone
  • Cyclic AMP
  • GTP-Binding Proteins
  • somatotropin releasing hormone receptor

Associated data

  • GENBANK/L07379
  • GENBANK/L07380