Yamada M, Monden T, Satoh T, Satoh N, Murakami M, Iriuchijima T, Kakegawa T, Mori M
First Department of Internal Medicine, Gunma University School of Medicine, Japan.
Biochem Biophys Res Commun. 1993 Sep 15;195(2):737-45. doi: 10.1006/bbrc.1993.2107.
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.
我们克隆了人促甲状腺激素释放激素受体(TRH-R)基因及其垂体cDNA,并研究了TRH-R mRNA是否在肢端肥大症患者的生长激素分泌性垂体腺瘤中表达并发挥功能。人TRH-R由398个氨基酸组成,是G蛋白偶联受体家族的成员。该基因在编码序列中有一个内含子。添加TRH可使表达该受体的中国仓鼠卵巢细胞内的钙浓度明显升高。尽管与人促甲状腺激素释放激素受体高度同源,但人促甲状腺激素释放激素受体在羧基末端结构上存在一些差异。序列和功能分析表明,垂体腺瘤中TRH-R mRNA的表达与正常垂体中的表达相同,这表明:1)一些肢端肥大症患者的腺瘤表达完整且有功能的TRH-R;2)患者中发现的生长激素分泌对TRH的矛盾反应可能是TRH对腺瘤中表达的TRH-R的直接作用。