Abstract
We have tested the hypothesis that adrenomedullin (ADM), a multifunctional peptide hormone, works as a trophoblast proinvasion factor. Our results showed that ADM receptor components-the mRNA and proteins of calcitonin receptor-like receptor (CALCRL) and receptor activity modifying proteins (RAMPs)-were expressed by human choriocarcinoma JAr cells and first-trimester cytotrophoblast HTR-8/SV neo cells. ADM stimulates both JAr and HTR-8/SV neo cell proliferation. The invasion capabilities of JAr cells and HTR-8/SV neo cells were also enhanced by ADM, and this was associated with increased gelatinolytic activity and reduced plasminogen activator inhibitor-1 mRNA expression (SERPINE1). Our data support the notion that ADM may be involved in the human implantation process via regulating trophoblast proliferation and differentiation.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adrenomedullin
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Calcitonin Receptor-Like Protein
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Cell Line
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Cell Proliferation
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Choriocarcinoma / pathology
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Female
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Fluorescent Antibody Technique
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Gene Expression Regulation / drug effects
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Humans
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Intracellular Signaling Peptides and Proteins / genetics
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Intracellular Signaling Peptides and Proteins / metabolism
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Matrix Metalloproteinase 2 / drug effects
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Matrix Metalloproteinase 2 / metabolism
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Matrix Metalloproteinase 9 / drug effects
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Matrix Metalloproteinase 9 / metabolism
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Membrane Proteins / genetics
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Membrane Proteins / metabolism
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Peptides / genetics
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Peptides / metabolism*
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Peptides / pharmacology
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Plasminogen Activator Inhibitor 1 / genetics
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Pregnancy
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Pregnancy Trimester, First
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RNA, Messenger / metabolism
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Receptor Activity-Modifying Proteins
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Receptors, Adrenomedullin
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Receptors, Calcitonin / genetics
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Receptors, Calcitonin / metabolism
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Receptors, Peptide / genetics
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Trophoblasts / cytology*
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Trophoblasts / drug effects
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Uterine Neoplasms / pathology
Substances
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CALCRL protein, human
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Calcitonin Receptor-Like Protein
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins
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Peptides
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Plasminogen Activator Inhibitor 1
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RNA, Messenger
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Receptor Activity-Modifying Proteins
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Receptors, Adrenomedullin
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Receptors, Calcitonin
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Receptors, Peptide
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SERPINE1 protein, human
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Adrenomedullin
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Matrix Metalloproteinase 2
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Matrix Metalloproteinase 9