Endocrine Abstracts (2002) 3 P283

Thyroid hormone (TH) regulation of iodothyronine deiodinase and thyroid hormone receptor (TR) expression in placental trophoblast cells

EL Hobbs1,2, P Driver1, CJ McCabe1, JA Franklyn1 & MD Kilby2

1Division of Medical Sciences, The University of Birmingham, Queen Elizabeth Hospital, Birmingham, UK; 2Division of Reproductive and Child Health, The University of Birmingham, Birmingham Women's Hospital, Birmingham, UK.

Subtle irregularity in maternal thyroid status during the 1st trimester of pregnancy is associated with abnormalities of neurodevelopment in childhood. Both iodothyronine deiodinase and TR expression in the fetoplacental unit are fundamental in controlling active TH delivery to the fetus. Using real time RT-PCR and gene specific Taqman probes and primers, we quantified mRNA expression of the deiodinase enzymes D2 and D3, and TRalpha1, TRalpha2 and TRbeta1 in the absence and presence of 3,3',5-triiodothyronine (T3) in human primary cultured villous cytotrophoblast cells and two placental choriocarcinoma cell lines (JEG-3 and BeWo). We demonstrated that all three cell types showed basal mRNA expression of D2, D3, TRalpha1, TRalpha2 and TRbeta1. Increasing T3 concentrations significantly upregulated primary cell D2 and D3 mRNA expression (0-100nM, n=8, p=0.005 & p=0.002 respectively). At 100nM, D2 mRNA expression was upregulated 2.5 fold (p=0.023) and D3 3 fold (p=0.014). In JEG-3 & BeWo cells, D3 mRNA expression was also significantly upregulated with increasing T3 (0-100nM, n=8 min, p=0.005 and p=0.021 respectively). At 100nM, JEG-3 D3 mRNA expression was upregulated 7-fold (p=0.063) and 3-fold in BeWo cells (p=0.012). In primary cells, basal mRNA expression of TRbeta1 was significantly lower (p<0.001) and D2 and D3 mRNA expression significantly higher (p<0.001) than the choriocarcinoma cell lines. We have demonstrated deiodinase and TR mRNA expression in both established choriocarcinoma cell lines and cultured primary placental cells. Both D2 and D3 mRNA expression is upregulated in these cell types by T3, indicating these enzymes may have a modulatory role in the transfer of T3 across the placenta.

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