Effects of corticotropin-releasing hormone and stresscopin on vascular endothelial growth factor mRNA expression in cultured early human extravillous trophoblasts.
Corticotropin-releasing hormone (CRH) takes a role in the regulation of the onset of parturition. Stresscopin (SCP) is a high affinity ligand for CRH receptor (CRHR)-2. CRHR-2 inhibits VEGF-induced neovascularization. In the present study, we investigated the effects of CRH and SCP on VEGF expression in early placental extravillous trophoblasts (EVTs). Isolation and culture of trophoblasts differentiating into EVTs were performed by the enzymatic digestion of anchoring early placental villi. The presence of CRH, SCP, CRHR-1, and CRHR-2 in cultured EVTs was examined by RT-PCR and immunocytochemistry. The effects of CRH and SCP on VEGF mRNA levels in cultured EVTs were assessed by real-time RT-PCR. CRH, SCP, CRHR-1, and CRHR-2 were expressed in cultured EVTs at mRNA and protein levels. Treatment with either 100 nM CRH or 100 nM SCP for 24 h decreased VEGF mRNA levels in cultured EVTs. The CRH- and SCP-induced decrease in VEGF mRNA levels was counteracted by the concomitant treatment with CRHR-2 antagonist antisauvagine-30, but not with CRHR-1 antagonist antalarmin. We demonstrated that CRH and SCP inhibited VEGF mRNA expression in cultured EVTs through the interaction with CRHR-2, suggesting that CRH and SCP may inhibit angiogenesis during early placentation.
Wakahashi
Senn
S
Department of Obstetrics and Gynecology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
Nakabayashi
Koji
K
Maruo
Nobuyuki
N
Yata
Ai
A
Ohara
Noriyuki
N
Maruo
Takeshi
T
D000328:Adult; D002478:Cells, Cultured; D003346:Corticotropin-Releasing Hormone / Q000096:biosynthesis / Q000494:pharmacology*; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D009215:Myometrium / Q000378:metabolism; D010920:Placenta / Q000166:cytology / Q000378:metabolism; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis; D018019:Receptors, Corticotropin-Releasing Hormone / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014327:Trophoblasts / Q000187:drug effects / Q000378:metabolism*; D054832:Urocortins / Q000096:biosynthesis / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*
D018076:DNA, Complementary; D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; C426704:UCN3 protein, human; D054832:Urocortins; D042461:Vascular Endothelial Growth Factor A; D003346:Corticotropin-Releasing Hormone