Dramatic elevation of plasma metastin concentrations in human pregnancy: metastin as a novel placenta-derived hormone in humans.
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.
Horikoshi
Yasuko
Y
Discovery Research Laboratories I, Pharmaceutical Division, Takeda Chemical Industries Ltd., Wadai, Tsukuba, Ibaraki 300-4293, Japan.
Matsumoto
Hirokazu
H
Takatsu
Yoshihiro
Y
Ohtaki
Tetsuya
T
Kitada
Chieko
C
Usuki
Satoshi
S
Fujino
Masahiko
M
D000328:Adult; D000911:Antibodies, Monoclonal; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D059648:Kisspeptins; D008297:Male; D010920:Placenta / Q000378:metabolism*; D049590:Postpartum Period / Q000378:metabolism; D011247:Pregnancy; D011506:Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D025521:Tumor Suppressor Proteins
D000911:Antibodies, Monoclonal; C106628:KISS1 protein, human; D059648:Kisspeptins; D011506:Proteins; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins