| RRC ID |
39441
|
| 著者 |
Miller TL, Godfrey PA, Dealmeida VI, Mayo KE.
|
| タイトル |
The rat growth hormone-releasing hormone receptor gene: structure, regulation, and generation of receptor isoforms with different signaling properties.
|
| ジャーナル |
Endocrinology
|
| 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.
|
| 巻・号 |
140(9)
|
| ページ |
4152-65
|
| 公開日 |
1999-9-1
|
| DOI |
10.1210/endo.140.9.6977
|
| PMID |
10465288
|
| MeSH |
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*
Receptors, Neuropeptide / physiology
Receptors, Pituitary Hormone-Regulating Hormone / genetics*
Receptors, Pituitary Hormone-Regulating Hormone / physiology
Signal Transduction / physiology
Transcription, Genetic / physiology
|
| IF |
3.934
|
| 引用数 |
67
|
| リソース情報 |
| ヒト・動物細胞 |
MtT/S(RCB0528) |
