| Co-Investigator(Kenkyū-buntansha) |
FUKUOKA Masatsune Kyoto University, Graduate School of Medicine, Assistant Professor, 医学研究科, 助手 (80243012)
KONISHI Ikuo Kyoto University, Graduate School of Medicine, Lecturer, 医学研究科, 講師 (90192062)
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| Budget Amount *help |
¥7,800,000 (Direct Cost: ¥7,800,000)
Fiscal Year 1997: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1996: ¥4,700,000 (Direct Cost: ¥4,700,000)
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| Research Abstract |
Angiotensin II (Ang II) acts on at least two receptor subtypes, type 1(AT1) and type 2(AT2). AT2 receptor expression is decreased during pregnancy, while that of the AT1 receptor is not. This down-regulation of the AT2 receptor, possibly mediated by sex steroids, may play a role in myometrial function and the maintenance of normal pregnancy in humans.
By treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA), HL-60 cells were transformed to macrophage-like cells, which secreted PAF-AH into the culture media time-and dose-dependently. Among the substances examined, cortisol and TGF-b, significantly and dose-dependently suppressed PAF-AH secretion from TPA-stimulated HL-60 cells. These results suggest that local PAF concentration in the pregnant uterus might be regulated, at least partly, by cortisol and TGF-b.
To elusidate the possible involvement of nitric oxide (NO) in parturition, we measured maternal plasma levels of NO metabolites (NOx) and cGMP.Plasma levels of cGMP and BOx signi
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ficantly decreased at vaginal delivery but not at Cesarean delivery. These changes were independent of plasma ANP and BNP levels, suggesting the possible down-regulation of maternal NO synthesis during parturition.
Prostaglandin (PG) E2 and PGF2a are believed to play important roles in the myometrial contraction and the initiation of labor. Myometrial contraction by these prostanoids is mediated mainly through EP3 and FP, which are specific receptors to PGE2 and PGF2a, respectively. The expressions of EP3 and FP genes were detected in all samples examined. During pregnancy, the expression of EP3 and FP genes in human myometrium was significantly reduced, to 50-60% of that in nonpregnant myometrium. The down-regulation of EP3 and FP during pregnancy may play a role in the relaxation of myometrium, and thus in the maintenance of normal pregnancy in humans.
Leptin is a novel hormone that is expressed abundantly and specifically in the adipose tissue. In the present study, we demonstrated non-adipose tissue production of leptin. Leptin is produced by placental trophoblasts and amnion cells from human pregnant uteri. In pregnant women, leptin was secreted from the placenta into the maternal circulation at a considerable amount comparable to those in non-pregnant obese women. Leptin was also present in feto-placental circulation. We also examined immunohistochemical localization of leptin and obese gene expression in molar tissues in 7 women with hydatidiform mole. Immunohistochemically, trophoblast cells were clearly stained for leptin. Northem blot analysis demonstrated augmented obese gene expression in molar tissue. The present study provides the first evidence for leptin as a novel placenta-derived hormone in humans and suggests the physiologic and pathophysiologic significance of leptin in normal and abnormal pregnancy. Less
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