Horikoshi Yasuko, Matsumoto Hirokazu, Takatsu Yoshihiro, Ohtaki Tetsuya, Kitada Chieko, Usuki Satoshi, Fujino Masahiko
Discovery Research Laboratories I, Pharmaceutical Division, Takeda Chemical Industries Ltd., Wadai, Tsukuba, Ibaraki 300-4293, Japan.
J Clin Endocrinol Metab. 2003 Feb;88(2):914-9. doi: 10.1210/jc.2002-021235.
Metastin is a novel peptide that was recently isolated from human placenta as the endogenous ligand of an orphan heptahelical receptor, hOT7T175. Metastin has been shown to suppress the motility of hOT7T175-transfected melanoma cells; however, studies of the physiological function of metastin have begun only recently. To investigate the possibility that metastin is an endocrine peptide, we determined the immunoreactive (ir-) metastin concentration in human plasma using our newly developed, sensitive, and specific two-site enzyme immunoassay. The plasma concentrations of ir-metastin in males and females were 1.30 +/- 0.14 (n = 12) and 1.31 +/- 0.37 fmol/ml (n = 10), respectively. As metastin is known to be abundant in human placenta, the ir-metastin concentration in the maternal plasma was then determined. The ir-metastin concentrations were 1230 +/- 346 fmol/ml (n = 11) in the first trimester, 4590 +/- 555 (n = 16) in the second trimester, and 9590 +/- 1640 (n = 12) in the third trimester. On d 5 after delivery, the ir-metastin concentration returned to nearly the nonpregnant level (7.63 +/- 1.33 fmol/ml; n = 10), suggesting that ir-metastin increases in pregnancy and is derived mainly from the placenta. The plasma from both nonpregnant and pregnant women showed a single ir-metastin peak at the same retention time as authentic metastin on reverse phase HPLC analysis, indicating that the major portion of the circulating metastin, as determined by our two-site enzyme immunoassay, represents endogenous metastin. Histochemical studies of human placenta localized metastin mRNA and immunoreactivity to the syncytiotrophoblasts. The present study provides evidence for metastin as a novel placenta-derived hormone in humans.
Metastin是一种新型肽，最近从人胎盘中分离出来，是一种孤儿七螺旋受体hOT7T175的内源性配体。已证明Metastin可抑制hOT7T175转染的黑色素瘤细胞的运动；然而，对Metastin生理功能的研究直到最近才开始。为了研究Metastin是一种内分泌肽的可能性，我们使用新开发的、灵敏且特异的双位点酶免疫分析法测定了人血浆中免疫反应性（ir-）Metastin的浓度。男性和女性血浆中ir-Metastin的浓度分别为1.30±0.14（n = 12）和1.31±0.37 fmol/ml（n = 10）。由于已知Metastin在人胎盘中含量丰富，随后测定了母体血浆中ir-Metastin的浓度。孕早期ir-Metastin的浓度为1230±346 fmol/ml（n = 11），孕中期为4590±555（n = 16），孕晚期为9590±1640（n = 12）。分娩后第5天，ir-Metastin浓度恢复到接近非妊娠水平（7.63±1.33 fmol/ml；n = 10），表明ir-Metastin在孕期升高且主要来源于胎盘。非妊娠和妊娠妇女的血浆在反相高效液相色谱分析中均显示出与真实Metastin相同保留时间的单个ir-Metastin峰，表明我们的双位点酶免疫分析法测定的循环Metastin的主要部分代表内源性Metastin。人胎盘的组织化学研究将Metastin mRNA和免疫反应性定位到合体滋养层细胞。本研究为Metastin作为一种新型人胎盘源激素提供了证据。
