Cortisol stimulates system A amino acid transport and SNAT2 expression in a human placental cell line (BeWo).
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 [(14)C]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 microM. 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.
Jones
Helen N
HN
Maternal-Fetal Physiology, Rowett Research Institute, Aberdeen, AB21 9SB, UK.
Ashworth
Cheryl J
CJ
Page
Ken R
KR
McArdle
Harry J
HJ
D000409:Alanine / Q000494:pharmacology; D026924:Amino Acid Transport System A / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D000621:Aminoisobutyric Acids / Q000378:metabolism; D001693:Biological Transport, Active / Q000187:drug effects; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D017097:Electric Impedance; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology*; D008094:Lithium / Q000494:pharmacology; D008353:Mannitol / Q000378:metabolism; D010920:Placenta / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D021381:Protein Transport / Q000187:drug effects
D026924:Amino Acid Transport System A; D000621:Aminoisobutyric Acids; C498797:SLC38A2 protein, human; C017911:2-(methylamino)isobutyric acid; D008353:Mannitol; D008094:Lithium; D000409:Alanine; D006854:Hydrocortisone