Effects of corticotropin-releasing hormone and stresscopin on vascular endothelial growth factor mRNA expression in cultured early human extravillous trophoblasts

Abstract

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.

Corticotropin Releasing Hormone and Urocortin 3 Stimulate Vascular Endothelial Growth Factor Expression through the cAMP/CREB Pathway

“…In rat vascular smooth muscle cells (SMCs), activation of CRHR2 by Ucn 2 treatment reduces VEGF expression levels (25). In contrast, CRH increases VEGF secretion in human mast cells and VEGF mRNA levels in human extravillous trophoblasts (30,31). Our study also demonstrated that VEGF levels were decreased in the colon of CRHR1-deficient mice with colitis but increased in the colon of CRHR2-deficient mice (29).…”

“…For instance, in rat smooth muscle cells, Ucn 1 inhibited VEGF release and consequently suppressed angiogenesis (25). Moreover, either CRH or Ucn 3 decreased VEGF mRNA expression levels in cultured early placental extravillous trophoblasts and this effect was counteracted by the CRHR2 antagonist antisauvagine-30 (31). Additionally, Ucn 1 and Ucn 2 suppressed VEGF expression in hepatocellular carcinoma and small cell lung carcinoma cells via CRHR2 (43,44).…”

Corticotropin-releasing factor family and its receptors: pro-inflammatory or anti-inflammatory targets in the periphery?

“…In particular, VEGF, as an important pro-inflammatory regulator and angiogenic regulator, was found to be regulated by CRFR2. It was shown that CRF inhibited VEGF mRNA expression in cultured early placental extravillous trophoblasts through interaction with CRFR2 [40]. It was also reported that VEGF level was decreased in rat smooth muscle cells (SMCs) by UCN 1 treatment via CRFR2 [41].…”

Corticotropin-Releasing Hormone As the Homeostatic Rheostat of Feto-Maternal Symbiosis and Developmental Programming In Utero and Neonatal Life

“…The diverse placental signaling mechanisms regulated by CRH suggest that elevated CRH controls the placental “surveillance and response” system so that the fetus can detect threats to survival and adjust its developmental trajectory (64–67) (Figure 2A). When stress signals (e.g., cortisol) from the maternal environment are detected by the fetoplacental unit, the “placental clock” may adapt by altering rate of synthesis of the “master” stress hormone, CRH.…”