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Structural and Functional Organization of the Gene Encoding the Human Thyrotropin‐Releasing Hormone Receptor
Author(s) -
Matre Vilborg,
Høvring Per Ivar,
Ørstavik Sigurd,
Frengen Eirik,
Rian Edith,
Velickovic Zlatibor,
MurrayMcIntosh Rosalind P.,
Gautvik Kaare M.
Publication year - 1999
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1999.0720040.x
Subject(s) - biology , intron , gene , exon , anterior pituitary , thyrotropin releasing hormone , reporter gene , genetics , regulatory sequence , microbiology and biotechnology , transcription (linguistics) , regulation of gene expression , gene expression , endocrinology , hormone , linguistics , philosophy
: The thyrotropin‐releasing hormone (TRH) receptor (TRHR)is widely distributed throughout the central and peripheral nervous systems.In addition to its role in controlling the synthesis and secretion ofthyroid‐stimulating hormone and prolactin from the anterior pituitary, TRH isbelieved to act as a neurotransmitter as well as a neuromodulator. We haveisolated genomic λ and P1‐derived artificial chromosome clones encodingthe human TRHR. The gene was found to be 35 kb with three exons and twointrons. A 541‐bp intron 1 (‐629 to ‐89 relative to the translation startsite) is conserved between human and mouse. A large intron 2 of 31 kb disruptsthe open reading frame (starting in position +790) in the sequence encodingthe supposed junction between the third intracellular loop and the putativesixth transmembrane domain. A similar intron was found in chimpanzee and sheepbut not in rat and mouse. Promoter analysis of upstream regions demonstratedcell type‐specific reporter activation, and sequencing of 2.5 kb of thepromoter revealed putative cis ‐acting regulatory elements for severaltranscription factors that may contribute to the regulation of the TRHR gene expression. Functional analysis of potential responseelements for the anterior pituitary‐specific transcription factor Pit‐1revealed cell type‐specific binding that was competed out with a Pit‐1response element from the GH gene promoter.