title: Adrenomedullin promotes rat trophoblast stem cell differentiation.
abstract: Accumulating data suggest that adrenomedullin (ADM) regulates the trophoblast cell growth, migration, and invasion. However, the effect of ADM on trophoblast differentiation is poorly understood. In this study, we hypothesized that ADM promotes the differentiation of trophoblast stem cells (TSCs) into trophoblast giant cells (TGCs). Using rat TSCs, Rcho-1 cells, we investigated the effect of ADM on TSC differentiation into TGCs in differentiation or stem cell media, respectively, and explored the effect of ADM on the mechanistic target of rapamycin (MTOR) signaling in trophoblast cell differentiation. The results include: 1) in the presence of differentiation medium, 10⁻⁷ M ADM, but not lower doses, elevated (P < 0.05) Prl3b1/Esrrb (i.e., the ratio of mRNA levels) by 1.7-fold compared to that in control; 2) the supplementation of ADM antagonist, regardless of the concentration of ADM, reduced (P < 0.05) Prl3b1/Esrrb by 2-fold, compared to control group, while the supplementation of CGRP antagonist, regardless of the concentration of ADM, did not change Prl3b1/Esrrb; 3) in the presence of stem cell medium, ADM did not alter the expression of TSC and TGC marker genes, however, the ratio of Prl3b1/Esrrb was reduced (P < 0.05) by ADM antagonist compared to that in control; and 4) ADM increased (P < 0.05) phosphorylated MTOR proteins and the ratio of phosphorylated to total MTOR proteins by 2.0- and 1.7-fold, respectively. The results indicate that ADM promotes but does not induce the differentiation of TSCs to TGCs in a dose-dependent manner and MTOR signaling may play a role in this process.
authors: Department of Obstetrics & Gynecology, Baylor College of Medicine, Houston, Texas.
authors: Haijun
authors: H
authors: Gao
authors: Department of Obstetrics & Gynecology, Baylor College of Medicine, Houston, Texas.
authors: Daniel A
authors: DA
authors: Liebenthal
authors: Department of Obstetrics & Gynecology, Baylor College of Medicine, Houston, Texas.
authors: Uma
authors: U
authors: Yallampalli
authors: Department of Obstetrics & Gynecology, Baylor College of Medicine, Houston, Texas cyallamp@bcm.edu.
authors: Chandra
authors: C
authors: Yallampalli
mesh_terms: D053607:Adrenomedullin / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D058286:Calcitonin Receptor-Like Protein / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D048429:Cell Size / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D051381:Rats; D058263:Receptor Activity-Modifying Protein 2 / Q000819:agonists* / Q000378:metabolism; D058265:Receptors, Adrenomedullin / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000737:chemistry / Q000378:metabolism; D014327:Trophoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000943:Antigens, Differentiation; D015415:Biomarkers; D058286:Calcitonin Receptor-Like Protein; C545580:Calcrl protein, rat; D010446:Peptide Fragments; C545509:Ramp2 protein, rat; D058263:Receptor Activity-Modifying Protein 2; D058265:Receptors, Adrenomedullin; C104782:adrenomedullin (22-52); C081830:adrenomedullin receptor, rat; C058636:calcitonin gene-related peptide (8-37); D053607:Adrenomedullin; C546845:mTOR protein, rat; D058570:TOR Serine-Threonine Kinases; D015740:Calcitonin Gene-Related Peptide
keywords: MTOR; Rcho-1 cell; adrenomedullin; differentiation; rat; trophoblast giant cell; trophoblast stem cell