Pituitary adenomas of patients with acromegaly express thyrotropin-releasing hormone receptor messenger RNA: cloning and functional expression of the human thyrotropin-releasing hormone receptor gene.
We cloned a human thyrotropin-releasing hormone receptor (TRH-R) gene and its pituitary cDNA, and examined whether TRH-R mRNA may be expressed and function in the GH-secreting pituitary adenomas of patients with acromegaly. The human TRH-R consists of 398 amino acids and is a member of the G protein-coupled receptor family. The gene has a single intron in the coding sequence. An addition of TRH caused an obvious increase in intracellular calcium concentration in chinese hamster ovary cells expressing this receptor. Although highly homologous to the rat and mouse TRH-Rs, the human TRH-R has several differences in the carboxyl-terminal structure. The sequence and functioning analyses showed the same expression of TRH-R mRNA in the pituitary adenomas as that in the normal pituitaries, indicating that 1) some adenomas of patients with acromegaly express an intact and functional TRH-R, and that 2) the paradoxical response of GH secretion to TRH found in the patients might be a direct effect of TRH on TRH-R expressed in the adenoma.
First Department of Internal Medicine, Gunma University School of Medicine, Japan.
M
M
Yamada
T
T
Monden
T
T
Satoh
N
N
Satoh
M
M
Murakami
T
T
Iriuchijima
T
T
Kakegawa
M
M
Mori
D000172:Acromegaly / Q000209:etiology / Q000378:metabolism*; D000236:Adenoma / Q000378:metabolism*; D000595:Amino Acid Sequence; D001483:Base Sequence; D015139:Blotting, Southern; D002118:Calcium / Q000378:metabolism; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D005091:Exons; D015870:Gene Expression; D015698:Genomic Library; D013006:Growth Hormone / Q000378:metabolism; D006801:Humans; D007438:Introns; D008297:Male; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D010902:Pituitary Gland / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000378:metabolism*; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis*; D017981:Receptors, Neurotransmitter / Q000096:biosynthesis* / Q000235:genetics*; D018025:Receptors, Thyrotropin-Releasing Hormone; D015183:Restriction Mapping; D013973:Thyrotropin-Releasing Hormone / Q000378:metabolism
D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D017981:Receptors, Neurotransmitter; D018025:Receptors, Thyrotropin-Releasing Hormone; D013973:Thyrotropin-Releasing Hormone; D013006:Growth Hormone; D004247:DNA; D002118:Calcium