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

Helen N Jones, Cheryl J Ashworth, Ken R Page, Harry J McArdle

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Both placental system A activity and fetal plasma cortisol concentrations are associated with intrauterine growth retardation, but it is not known if these factors are mechanistically related. Previous functional studies using hepatoma cells and fibroblasts produced conflicting results regarding the regulation of system A by cortisol. Using the b30 BeWo choriocarcinoma cell line, we investigated the regulation of system A by cortisol. System A function was analyzed using methyl amino isobutyric acid ( MeAIB) transcellular transport studies. Transporter expression [ system A transporter (SNAT)1/2] was studied at the mRNA and protein levels using Northern and Western blotting, respectively. Localization was carried out using immunocytochemistry. The [C-14] MeAIB transfer rate across BeWo monolayers after preincubation with cortisol for 24 h was significantly increased compared with control. This was associated with a relocalization of the SNAT2 transporter at lower cortisol levels and significant upregulation of mRNA and protein expression levels at cortisol levels > 1 mu M. This is the first study to show functional and molecular regulation of system A by cortisol in BeWo cells. It is also the first study to identify which system A isoform is regulated. These results suggest that cortisol may be involved in upregulation of system A in the placenta to ensure sufficient amino acid supply to the developing fetus.

Original languageEnglish
Pages (from-to)E596-E603
Number of pages8
JournalAmerican Journal of Physiology: Endocrinology and Metabolism
Volume291
Issue number3
Early online date18 Apr 2006
DOIs
Publication statusPublished - 15 Aug 2006

Keywords

  • alanine
  • amino acid transport system A
  • aminoisobutyric acids
  • biological transport, active
  • cell line, tumor
  • cell membrane
  • electric impedance
  • female
  • gene expression
  • humans
  • hydrocortisone
  • lithium
  • mannitol
  • placenta
  • pregnancy
  • protein transport

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