ITOH Hiroaki Kyoto University, Graduate School of Medicine, Department of Gynecology and Obst, 医学研究科, 助手 (70263085)
KONISHI Ikuo Kyoto University, Graduate School of Medicine, Department of Gynecology and Obst, 医学研究科, 講師 (90192062)
小林 史典 京都大学, 医学部, 助手 (00243022)
伊原 由幸 京都大学, 医学部, 講師 (10223299)
|Budget Amount *help
¥6,400,000 (Direct Cost : ¥6,400,000)
Fiscal Year 1995 : ¥2,200,000 (Direct Cost : ¥2,200,000)
Fiscal Year 1994 : ¥4,200,000 (Direct Cost : ¥4,200,000)
To elucidate the role of amnion and decidua tissues in the maintenance of human pregnancy, the production of endothelin (ET) and brain natriuretic peptide (BNP), and the expression of receptors for these peptides in intrauterine tissues were investigated. In addition, we examined the physiological role of phospholipase D (PLD) in amnion.
The ET production by cultured amnion cells was stimulated by various cytokines and growth factors present in amniotic fluid. Ligand binding analysis and Northern blot analysis indicated that both ET-A receptor and ET-B receptor are present in chorion laeve, decidua vera, and myometrium, but not in the amnion tissue at term. However, amnion tissue in the second trimester expressed ET-A receptor.
The BNP production by cultured amnion cells was dose-dependently stimulated by TGF-beta, but was inhibited by cortisol or EGF.The TGF-beta augmented BNP production was blocked by the simultaneous treatment with cortisol or EGF.The receptor for BNP (particulate gua
nylate cyclase A-type : GC-A) was identified in chorion, decidua, and myometrium by both cGMP generation assay and Northern blot analysis. However, GC-A was not detected in amnion tissues in the second trimester and at term. Thus, BNP secreted from amnion cells may not act on amnion tissue, but on the decidua and myometrium, and generate cGMP,the second messenger of BNP,and finally block uterine contraction during the second trimester. Such an inhibition of uterine contraction by BNP may be attenuated at term when the BNP secretion from amnion cells are suppressed by cortisol and EGF.
We previously reported the presence and biochemical characteristics of PLD in amnion rissue. The PLD activity in cultured amnion cells has been shown to be regulated by protein kinase C and Ca^<2+>. Phosphatidic acid (PA), the primary product of PLD,stimulated the PGE_2 secretion from cultured amnion cells. Moreover, PLD enhanced the ET secretion and inhibited the BNP secretion from cultured amnion cells. Thus, PLD plays important roles in the regulation of function of amnion cells and maintenance of human pregnancy.
In conclusion, various bioactive substances in the amniotic fluid of fetal origin act on amniotic membrane, modulate the production of ET,BNP,PA or PGE_2, and finally regulate the uterine contractility, v.i.z.the maintenance of pregnancy. Less