Cloning and functional characterisation of the human TRH receptor.
Thyrotrophin-releasing hormone (TRH) is a hypothalamic tripeptide known to act via its receptor in the anterior pituitary gland to stimulate the release of thyrotrophin (TSH) from thyrotrophs and prolactin (PRL) from lactotrophs. It is also thought to act as a neurotransmitter/neuromodulator in the central and peripheral nervous systems. We have isolated a cDNA encoding the human pituitary TRH receptor (TRH-R) protein with a predicted amino acid sequence of 398 amino acids. Comparison of the amino acid sequences of the human TRH-R with the previously published rodent TRH-Rs showed that it is similar to both the rat and mouse TRH-Rs, except that each species has variant amino acids at the carboxy (COOH) terminus. The human TRH-R belongs to the family of seven transmembrane domain, G-protein-coupled receptors, and it is believed that the COOH terminal region of this family of receptors may play an important role in receptor downregulation/internalisation, and possibly G-protein coupling. COS-1 cells expressing the human TRH-R showed high affinity receptor binding. Stimulation of these cells with TRH produced a typical phosphoinositide response and mobilisation of intracellular calcium [Ca2+]i.
Duthie
S M
SM
MRC Reproductive Biology Unit, Centre for Reproductive Biology, Edinburgh, UK.
Taylor
P L
PL
Anderson
L
L
Cook
J
J
Eidne
K A
KA
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D005796:Genes; D006801:Humans; D051379:Mice / Q000235:genetics; D008969:Molecular Sequence Data; D005810:Multigene Family; D051381:Rats / Q000235:genetics; D018025:Receptors, Thyrotropin-Releasing Hormone / Q000096:biosynthesis / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D014162:Transfection
D018076:DNA, Complementary; D018025:Receptors, Thyrotropin-Releasing Hormone; D011993:Recombinant Fusion Proteins