Adrenomedullin production is increased in normal human pregnancy

Iorio, Raffaele; Marinoni, Emanuela; Letizia, Claudio; Villaccio, Barbara; Alberini, Alessandro; Cosmi, E. V.

doi:10.1530/eje.0.1400201

Cited by 61 publications

(45 citation statements)

References 28 publications

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“…However, a recent report revealed no significant difference in mean maternal plasma concentrations of AM from week 8 to week 40 of pregnancy (14). The probable reasons for this discrepancy are the different hAM antibodies used in the RIAs, and the wide standard deviation of hAM concentrations as a result of the small sample size of our study.…”

Section: Discussioncontrasting

confidence: 71%

Immunoreactive adrenomedullin (AM) concentration in maternal plasma during human pregnancy and AM expression in placenta

Kobayashi

Kubota²,

T³

et al. 2000

European Journal of Endocrinology

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Adrenomedullin (AM) is a novel vasorelaxant peptide, isolated from human pheochromocytoma. Although AM may be involved in the regulation of the cardiovascular system, a number of other mechanisms are also involved. The present study was undertaken to confirm the presence of AM in human maternal circulation and in placental function during pregnancy. Immunoreactive (ir) AM concentrations in maternal plasma were 3.4 Ϯ 0.7 fmol/ml (mean Ϯ S.E.M.) in the first trimester, 3.3 Ϯ 1.1 fmol/ml in the second trimester, 7.3 Ϯ 2.8 fmol/ml in the third trimester, 4.1 Ϯ 1.9 fmol/ ml in early puerperium and 3.0 Ϯ 0.4 fmol/ml in non-pregnant periods; the concentration in the third trimester was significantly greater than those in other periods. Plasma concentrations of estradiol (E 2 ), progesterone, human placental lactogen (hPL) and human chorionic gonadotropin (hCG) were also measured, using RIA kits. Significant correlations have been demonstrated between the concentrations of irAM and those of E 2 , progesterone and hPL. We therefore examined the expression of AM within the placental tissues using immunohistochemistry and northern blot analysis in order to demonstrate a correlation between the presence of AM in the placenta and maternal plasma. Using immunohistochemistry, we detected AM in the amnion at term and the expression of AM mRNA in human placental tissues using cloned human (h) AM complementary DNA as a probe. This study demonstrates the immunoreactivity of human hAM in maternal plasma during pregnancy, and suggests that hAM in maternal plasma is generated partly from placental tissue.

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Section: Discussioncontrasting

confidence: 71%

Immunoreactive adrenomedullin (AM) concentration in maternal plasma during human pregnancy and AM expression in placenta

Kobayashi

Kubota²,

T³

et al. 2000

European Journal of Endocrinology

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“…9,10 We and others have shown a progressive increase in maternal plasma ADM levels throughout pregnancy. [11][12][13][14][15][16] In PE, early reports suggested that maternal ADM levels were decreased, but subsequent larger series found no difference from controls. 14,17,18 However, we believe that this indicates a lack of compensatory increase in response to the hypertensive state.…”

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confidence: 99%

Adrenomedullin Is Decreased in Preeclampsia Because of Failed Response to Epidermal Growth Factor and Impaired Syncytialization

Dakour

Kaufman

et al. 2003

Hypertension

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Abstract-To explore the mechanisms of adrenomedullin (ADM) regulation in normal and preeclamptic (PE) states, we determined placental production of ADM and ADM regulation by cytokines. Isolated, purified cytotrophoblast cultures from normal (nϭ8) and PE (nϭ10) placentas were cultured for 3 days in the absence or presence of 10 ng/mL epidermal growth factor (EGF), 1 ng/mL transforming growth factor (TGF)-␤1, 10 ng/mL tumor necrosis factor (TNF)-␣, or 100 U/mL interferon (IFN)-␥. Cells were also cultured for 3 days in 10% fetal bovine serum for determination of syncytial formation by desmoplakin staining. Pieces of normal and PE placentas were snap-frozen for ADM mRNA measurement. Results showed that basal ADM production into culture medium by radioimmunoassay was significantly lower in PE placental cells. EGF significantly stimulated ADM production in normal trophoblasts but did not in PE placentas.

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“…The concentration of ADM in maternal plasma increases during pregnancy in the human. 16,17 Furthermore, fetoplacental tissues appear to be an additional site of synthesis of ADM during pregnancy. 18 The role of ADM in the pathophysiology of preeclampsia is complex.…”

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confidence: 99%

Effect of Adrenomedullin on Placental Arteries in Normal and Preeclamptic Pregnancies

et al. 2001

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Abstract-Adrenomedullin is a potent vasodilatory peptide with plasma levels that increase during pregnancy. Although fetoplacental adrenomedullin levels are reported to increase in preeclampsia, maternal plasma levels may be elevated or decreased, or they may resemble those in normal pregnancy. In other hypertensive conditions, adrenomedullin increases. Therefore, we hypothesized that maternal plasma adrenomedullin levels would be higher in hypertensive pregnancies than in normotensive pregnancies and that the higher placental resistance found in preeclamptic pregnancies results from blunted activity of adrenomedullin on the vasculature. Adrenomedullin concentrations in plasma from women with normotensive pregnancies, gestational hypertension, and preeclampsia were determined by radioimmunoassay. Stem villous arteries from normotensive and preeclamptic pregnancies were dissected and mounted on a wire myograph system. Arteries were first preconstricted to 80% of their maximum constriction with U46619, a thromboxane A 2 mimetic, and exposed to cumulative doses of adrenomedullin (1ϫ10 Ϫ9 to 3ϫ10 Ϫ7 mol/L). Contrary to our hypothesis, there were no significant differences in maternal plasma adrenomedullin levels among patients with normal pregnancies, gestational hypertension, and preeclampsia. Adrenomedullin significantly relaxed arteries from both normal and preeclamptic placentas, but there was no significant difference between the 2 groups. During normal pregnancy, adrenomedullin may contribute to the low placental vascular resistance. This pathway appears to be intact in preeclampsia. We conclude that the increased placental vascular resistance observed in preeclampsia is due neither to reduced adrenomedullin secretion nor to an attenuated vascular responsiveness. Moreover, unlike other hypertensive disorders, there is no compensatory rise in circulating adrenomedullin levels. (Hypertension. 2001;37:227-231.)

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Adrenomedullin production is increased in normal human pregnancy

Cited by 61 publications

References 28 publications

Immunoreactive adrenomedullin (AM) concentration in maternal plasma during human pregnancy and AM expression in placenta

Immunoreactive adrenomedullin (AM) concentration in maternal plasma during human pregnancy and AM expression in placenta

Adrenomedullin Is Decreased in Preeclampsia Because of Failed Response to Epidermal Growth Factor and Impaired Syncytialization

Effect of Adrenomedullin on Placental Arteries in Normal and Preeclamptic Pregnancies

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