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

Abstract

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.

Reduced maternal expression of adrenomedullin disrupts fertility, placentation, and fetal growth in mice

“…Yet one of the greatest increases in plasma AM levels occurs during the course of a normal pregnancy, when plasma levels of the peptide, secreted by the placenta, are 4- to 5-fold higher by the third trimester (21,(29)(30)(31)(32) and rapidly return to pre-pregnancy values after delivery (21). As recently reviewed by Wilson et al and Di Iorio et al, numerous clinical studies have attempted to correlate altered AM levels with a variety of pregnancy complications, including preeclampsia, spontaneous abortion, gestational diabetes, and FGR (33,34).…”

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

“…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.…”

Adrenomedullin in mammalian embryogenesis

“…Different research groups have shown elevated levels of AM in plasma of pregnant women at term (from 3-to 5-fold increase), as compared to levels in non-pregnant women or levels in the early puerperium Kanenishi et al, 2001;Kobayashi et al, 2000). Other vasoactive substances, such as endothelin, prostaglandin E2, and prostacyclin, have also been reported to increase in maternal plasma in a similar fashion (Brennecke et al, 1985;Goodman et al, 1982;Mastrogiannis et al, 1991).…”

“…Occasionally, immunocytochemical staining for AM has also been reported in cytotrophoblast cells and in the mesenchyma and inflammatory cells within the villi (Kanenishi et al, 2001;Macri et al, 1998). The fetal membranes, and, more specifically, the epithelium of the amniotic membrane, also show high levels of AM and its mRNA (Kanenishi et al, 2000(Kanenishi et al, , 2001Kobayashi et al, 2000;Macri et al, 1996b;Makino et al, 1999c). The pattern and intensity of AM immunoreactivity in the first trimester human placenta and fetal membranes were reported to be similar to that in term pregnancy (Macri et al, 1996a;Kanenishi et al, 2001), suggesting that AM secreted from these sites might play an important role in the maintenance of normal pregnancy throughout gestation.…”

“…Other vasoactive substances, such as endothelin, prostaglandin E2, and prostacyclin, have also been reported to increase in maternal plasma in a similar fashion (Brennecke et al, 1985;Goodman et al, 1982;Mastrogiannis et al, 1991). However, when comparing AM concentrations in plasma throughout pregnancy, some investigators have found no significant changes between different periods , whereas others have reported increasing concentrations with advancing gestation (Kanenishi et al, 2001), or significant increases only in the third trimester (Kobayashi et al, 2000).…”