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and RAR
) mRNA determined by real-time quantitative RT-PCR in peripheral blood mononuclear cells of hypothyroid patients
1 Unité de Nutrition et Signalisation Cellulaire (E.A. MENRT, Usc INRA) ISTAB, Avenue des Facultés Université Bordeaux 1, 33405 Talence, France
2 Service de Biochimie de lHôpital Pellegrin, Centre Hospitalier Universitaire de Bordeaux, Place Amélie Raba Léon, 33000 Bordeaux, France
3 Service dEndocrinologie, Diabétologie et Maladies Métaboliques de lHôpital Haut-Levêque, Centre Hospitalier Universitaire de Bordeaux, Avenue Magellan, 33600 Pessac, France
(Requests for offprints should be addressed to V Pallet; Email: v.pallet{at}istab.u-bordeaux1.fr)
In vivo assessment of the cellular impact of thyroid hormones on target tissues might be of help for physiological studies and to evaluate the consequences of various diseases of the thyroid gland in humans. Given the tenuous relationship between retinoid and tri-iodothyronine (T3) status and that retinoids have also intracellular roles, the aim of this study was to determine the effect of hypothyroidism on the expression of T3 nuclear receptors (TR) and retinoic acid nuclear receptors (RAR, RXR) in human peripheral blood mononuclear cells (PBMC). Using real time RT-PCR, we quantified the relative amount of mRNA of the thyroid (TR
and TRß) and retinoid (RAR
, RAR
, and RXR
) nuclear receptors in PBMC of euthyroid (n=22) compared with hypothyroid (n=22) subjects. Classical plasma parameters (free T3 (FT3), free thyroxine (T4) (FT4), thyroid-stimulating hormone (TSH), retinol (ROH), retinol-binding protein (RBP) and transthyretin (TTR)) were also measured. In hypothyroid subjects, the concentration of TSH was elevated, and dramatically low T3 and T4 concentrations were associated with a decrease in the expression of TRß. Expression of RAR
and RAR
significantly decreased in hypothyroid versus control subjects, while an increased concentration of ROH was emphasised by hypothyroidism. These results first indicated that primary hypothyroidism induces hypoactivation of the retinoid nuclear pathway in PBMC, which was not predicted by the plasma ROH level. Further investigations will be necessary to evaluate these parameters in very small changes in thyroid hormone production such as mild (subclinical) hypothyroidism.
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