Adrenomedullin in mammalian embryogenesis

Abstract

Here are summarized data supporting that adrenomedullin (AM) is a multifunctional factor involved in the complex regulatory mechanisms of mammalian development. During rodent embryogenesis, AM is first expressed in the heart, followed by a broader but also defined spatio-temporal pattern of expression in vascular, neural, and skeletal-forming tissues as well as in the main embryonic internal organs. AM pattern of expression is suggestive of its involvement in the control of embryonic invasion, proliferation, and differentiation processes, probably through autocrine or paracrine modes of action. AM levels in fetoplacental tissues, uterus, maternal and umbilical plasma are highly increased during normal gestation. These findings in addition to other physiological and gene targeting studies support the importance of AM as a vasorelaxant factor implicated in the regulation of maternal vascular adaptation to pregnancy, as well as of fetal and fetoplacental circulations. AM is also present in amniotic fluid and milk, which is suggestive of additional functions in the maturation and immunological protection of the fetus. Altered expression of AM has been found in some gestational pathologies, although it is not yet clear whether this corresponds to causative or compensatory mechanisms. Future studies in regard to the distribution and expression levels of the molecules known to function as AM receptors, together with data on the action of complement factor H (an AM binding protein), may help to better define the roles of AM during embryonic development.

The Proinflammatory Cytokine Interleukin 1β and Hypoxia Cooperatively Induce the Expression of Adrenomedullin in Ovarian Carcinoma Cells through Hypoxia Inducible Factor 1 Activation

“…In addition, ADM and ADM-Rs were shown to be ubiquitously expressed during embryogenesis. Especially maternal decidual cells and embryonic cytotrophoblast cells show high levels of ADM and ADM-R expression and it has been reasoned that ADM might facilitate the invasion of cells (30)(31)(32). With respect to carcinogenesis, ADM may be involved in a similar process during tumor cell invasion (33).…”

“…Ten micrograms of nuclear extracts were preincubated on ice for 20 minutes in a binding-buffer [12 mmol/L HEPES (pH 7.9), 4 mmol/L Tris-HCl (pH 7.9), 60 mmol/L KCl, 1 mmol/L EDTA, 1 mmol/L DTT] with 100 ng thymus DNA. After the addition of [g- 32 P]ATP, the samples were incubated for 30 minutes at room temperature. For supershift assays, the samples were additionally incubated with an anti-HIF-1a monoclonal antibody (Transduction Laboratories) for 16 hours at 4jC.…”

Adrenomedullin gene expression differences in mice do not affect blood pressure but modulate hypertension-induced pathology in males

“…The gene coding for AM is widely expressed throughout the body, most highly in endothelial cells and vascular smooth muscle cells (2,3). Consequently, highly vascularized tissues, such as the placenta, lung, heart, and kidney cause elevated plasma AM levels when their secretion of AM peptide is stimulated by conditions such as pregnancy, sepsis, and cardiovascular disease or by inflammatory cytokines or hypoxia.…”

Trophoblast Invasion and Uterioimplantation Growth in Early Rat Gestation Requisite Adrenomedullin

“…Currently, ADM has been concerned in a multiplicity of reproductive functions, specifically during pregnancy. In the human, plasma ADM levels were raised during pregnancy and reduced at term [1][2][3][4]. This augmentation in ADM levels happened immediately after implantation, and subsequently, decrease of ADM took place in both plasma [5,6] and amniotic fluid [7] later in gestation.…”

“…The blastocyst signals that induce the apoptotic cascade, as well as the genes that regulate this local event, are still unknown. Recent reports suggest that AM is a regulator of cell growth and differentiation [4] and that it plays a potent protective role against apoptosis and in maintaining cellular integrity. Hence, normal ADM function is required to prevent apoptosis and sustain normal implantation, placental development, and fetal growth.…”