HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

The rat growth hormone-releasing hormone receptor gene: structure, regulation, and generation of receptor isoforms with different signaling properties.

Abstract
The interaction of GHRH with membrane-bound receptors on somatotroph cells of the anterior pituitary is an important step in the regulation of GH synthesis and secretion. The identification of a G protein-coupled receptor for GHRH has made it possible to investigate the pathway by which GHRH regulates pituitary somatotroph cell function. To initiate an analysis of the mechanisms regulating expression and function of the GHRH receptor, the structure of the gene and its promoter region were analyzed. The coding sequence of the rat GHRH receptor gene is contained within 14 exons spanning approximately 15 kb of genomic DNA. Four transcription start sites are located within 286 bp upstream of the initiation codon. The 5' flanking region of the GHRH receptor gene acts as a functional promoter in rat pituitary tumor GH3 cells, and basal promoter activity is enhanced in GH3 and COS7 cells by cotransfection of an expression construct encoding the pituitary-specific transcription factor Pit-1. The rat GHRH receptor gene is subject to at least 1 alternative RNA processing event that generates 2 receptor isoforms differing by 41 amino acids within the third intracellular loop (IL) of the protein. The short isoform of the GHRH receptor is predominant in pituitary cells. The MtT/S pituitary tumor cell line was found to express the GHRH receptor, and different populations of these cells produce predominantly the long or short isoforms of the receptor messenger RNA, suggesting that the alternative splicing can be regulated. Functional analysis of the two GHRH receptor isoforms demonstrates that both bind GHRH, but only the short isoform signals through a cAMP-mediated pathway. Neither receptor isoform is able to stimulate calcium mobilization from internal stores after GHRH treatment. Our findings indicate that the pituitary-specific transcription factor Pit-1 is involved in the somatotroph-specific expression of the GHRH receptor gene and that functionally distinct receptor proteins are generated by an alternative RNA processing mechanism.
AuthorsT L Miller, P A Godfrey, V I Dealmeida, K E Mayo
JournalEndocrinology (Endocrinology) Vol. 140 Issue 9 Pg. 4152-65 (Sep 1999) ISSN: 0013-7227 [Print] United States
PMID10465288 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Protein Isoforms
  • Receptors, Neuropeptide
  • Receptors, Pituitary Hormone-Regulating Hormone
  • somatotropin releasing hormone receptor
Topics
  • Amino Acid Sequence (genetics)
  • Animals
  • Base Sequence (genetics)
  • Exons (genetics)
  • Gene Expression Regulation (physiology)
  • Genome
  • Male
  • Molecular Sequence Data
  • Promoter Regions, Genetic (genetics)
  • Protein Isoforms (physiology)
  • Rats (genetics)
  • Rats, Sprague-Dawley
  • Receptors, Neuropeptide (genetics, physiology)
  • Receptors, Pituitary Hormone-Regulating Hormone (genetics, physiology)
  • Signal Transduction (physiology)
  • Transcription, Genetic (physiology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: