Cortisol stimulates system A amino acid transport and SNAT2 expression in a human placental cell line (BeWo)

Jones, Helen; Ashworth, Cheryl; Page, K R; McArdle, Harry J

doi:10.1152/ajpendo.00359.2005

Cited by 72 publications

(40 citation statements)

References 35 publications

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“…The functional role of SNAT2, a neutral amino acid transporter, has been extensively described in placental tissues of different species and in human placental cells in vitro (13,(16)(17)(18)(19).…”

Section: Discussionmentioning

confidence: 99%

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SNAT2 expression and regulation in human growth-restricted placentas

et al. 2013

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Background: Amino acid placental delivery is reduced in human intrauterine growth-restricted (IUGR) fetuses, and the activity of placental amino transporters has been consistently shown to be decreased in in vitro studies. We hypothesized lower placental expression and localization of sodium-coupled neutral amino acid transporter 2 (SNAT2 (also known as SLC38A2)), altered levels of intron-1 methylation, and altered distribution of single-nucleotide polymorphisms in human IUGR vs. normal pregnancies. Methods: We studied 88 IUGR and 84 control placentas from singleton pregnancies at elective caesarean section. SNAT2 expression was investigated by real-time PCR and immunohistochemistry. Intron-1 methylation levels were analyzed by pyrosequencing, and single-nucleotide polymorphism distribution was analyzed by allelic discrimination. results: mRNA levels were significantly decreased in IUGR placentas with reduced umbilical blood flows. Syncytiotrophoblast immunostaining was lower in IUGR placentas than in control placentas. Methylation levels were steadily low in both IUGR and control placentas. SNP genotype and allele frequencies did not differ between the two groups. conclusion: This is the first study investigating SNAT2 expression and regulation mechanisms in human IUGR placentas. We confirm previous results obtained in rats and cell cultures that support the fundamental role of SNAT2 in fetal growth and well-being, as well as a possible role of oxygen levels in regulating SNAT2 expression, indicating the relevance of hypoxia in IUGR.

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Section: Discussionmentioning

confidence: 99%

“…Snat2 regulation is mediated by several factors (13,(16)(17)(18)(19), particularly hypoxia and amino acid extracellular concentrations. SNAT2 intron-1 is a noncoding region within the SNAT2 gene that spans 54 nucleotides and contains sequences that are able to respond to amino acid deficiency and activate SNAT2 gene expression (20).…”

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confidence: 99%

SNAT2 expression and regulation in human growth-restricted placentas

et al. 2013

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“…Cortisol promotes the development and function of the placenta, through enhanced differentiation and upregulated nutrient transport (Nacharaju et al 2004, Jones et al 2006. Therefore, reduced cortisol at day 45, and lower placental GR may compromise placental development and function in small fetuses.…”

Section: Discussionmentioning

confidence: 99%

Glucocorticoid exposure and tissue gene expression of 11β HSD-1, 11β HSD-2, and glucocorticoid receptor in a porcine model of differential fetal growth

McNeil¹,

Nwagwu²,

Finch³

et al. 2007

Reproduction

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Glucocorticoids play a critical role in fetal development, but inappropriate exposure is associated with reduced fetal growth. We investigated cortisol exposure and supply in a porcine model of differential fetal growth. This model compares the smallest fetus of a litter with an average-sized sibling at three stages of gestation. At day 45, small fetuses had reduced plasma cortisol (16.8G 3.4 ng/ml) relative to average fetuses (34.4G3.4 ng/ml, P!0.001). At day 65 levels had reduced in small and average fetuses to similar concentrations (5.7G1.0 vs 4.8G0.5 ng/ml, PZ0.128). By day 100, elevated levels were found in small fetuses (10.7G1.5 vs 7.6G0.7 ng/ml, P!0.001). Maternal plasma cortisol was unchanged over gestation (day 45, 56.7G21.6 ng/ml; day 65, 57.8G 14.4 ng/ml; day 100, 55.7G6.5 ng/ml). We examined the cause of altered cortisol by investigating the fetal hypothalamicpituitary-adrenal axis through the measurement of adrenocorticotropic hormone and assessing exposure to maternal cortisol by quantifying placental 11b-hydroxysteroid dehydrogenase-isoform 2 (11b HSD-2) gene expression. These data suggest that altered cortisol supply was of fetal origin. We examined organ glucocorticoid (GC) metabolism by the measurement of GC receptor (GR) and 11b-hydroxysteroid dehydrogenase-isoform 1 (11b HSD-1) gene expression. We found that fetal organs have different temporal patterns of 11b HSD-1 and GR expression, with the liver particularly sensitive to cortisol in late gestation. This study examines GC exposure in naturally occurring differential growth and simultaneously explores tissue GC sensitivity and handling, at three key stages of gestation. Reproduction (2007) 133 653-661

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“…System A is subjected to extensive regulation, and, in the placenta, it has been shown to be inhibited by IL-1␤ (64), hypoxia (48), nitric oxide (NO) formation (37), hyperglycemia (21), and growth hormone (20). Insulin (27,36), IGF-I (35), EGF (5), amino acid deprivation (34), cortisol (33), and leptin (27) all stimulate system A transport. The regulation of placental system L and TAUT is less well established.…”

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confidence: 99%