The present address of Dr. E. Frengen is Biotechnology Center Oslo, University of Oslo, P. O. Box 1125 Blindern, N-0317 Oslo, Norway.
Structural and Functional Organization of the Gene Encoding the Human Thyrotropin-Releasing Hormone Receptor
Article first published online: 18 JAN 2002
Journal of Neurochemistry
Volume 72, Issue 1, pages 40–50, January 1999
How to Cite
Matre, V., Høvring, P. I., Ørstavik, S., Frengen, E., Rian, E., Velickovic, Z., Murray-McIntosh, R. P. and Gautvik, K. M. (1999), Structural and Functional Organization of the Gene Encoding the Human Thyrotropin-Releasing Hormone Receptor. Journal of Neurochemistry, 72: 40–50. doi: 10.1046/j.1471-4159.1999.0720040.x
The present address of Drs. Z. Velickovic and R. P. Murray-McIntosh is Department of Pathology, Wellington School of Medicine, Wellington, New Zealand.
Abbreviations used : CAT, chloramphenicol acetyltransferase ; EMSA, electrophoretic mobility shift assay ; GPCR, G protein-coupled receptor ; ORF, open reading frame ; PAC, P1-derived artifical chromosome ; PRL, prolactin ; TRH, thyrotropin-releasing hormone ; TRHR, TRH receptor ; 5′-UTR, 5′-untranslated region.
- Issue published online: 18 JAN 2002
- Article first published online: 18 JAN 2002
- Thyrotropin-releasing hormone receptor;
- Human gene;
- Large intron;
Abstract : 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 of thyroid-stimulating hormone and prolactin from the anterior pituitary, TRH is believed to act as a neurotransmitter as well as a neuromodulator. We have isolated genomic λ and P1-derived artificial chromosome clones encoding the human TRHR. The gene was found to be 35 kb with three exons and two introns. A 541-bp intron 1 (-629 to -89 relative to the translation start site) is conserved between human and mouse. A large intron 2 of 31 kb disrupts the open reading frame (starting in position +790) in the sequence encoding the supposed junction between the third intracellular loop and the putative sixth transmembrane domain. A similar intron was found in chimpanzee and sheep but not in rat and mouse. Promoter analysis of upstream regions demonstrated cell type-specific reporter activation, and sequencing of 2.5 kb of the promoter revealed putative cis-acting regulatory elements for several transcription factors that may contribute to the regulation of the TRHR gene expression. Functional analysis of potential response elements for the anterior pituitary-specific transcription factor Pit-1 revealed cell type-specific binding that was competed out with a Pit-1 response element from the GH gene promoter.