Abstract
Acute illness in mice profoundly affects hypothalamic type 2 deiodinase (D2) and thyrotropin-releasing hormone (TRH) mRNA expression. TRH expression is regulated by T3, predominantly via the thyroid hormone receptor (TR)-?. It is unknown at present whether hypothalamic D2 expression is mediated via the TR? as well. To study the role of TR? in hypothalamic thyroid hormone metabolism during acute illness we studied D2, type 3 deiodinase (D3) and TRH expression in TR?-/- and wild type (129/Sv) mice after bacterial endotoxin (LPS) administration. Mice were killed at 4, 8 and 24h after LPS; TRH, D2 and D3 mRNA expression was measured in the hypothalamic paraventricular nucleus (PVN). D2 mRNA expression was also measured in the arcuate nucleus region (ARC). Serum T3 and T4 was measured using RIA. Basal T3 and T4 levels were 2-3 fold higher in TR?-/- mice compared to WT while hypothalamic TRH, D2 and D3 mRNA expression was similar. LPS lowered serum T3 and T4 within 24h to the same extent in TR?-/- and WT mice. TRH expression in the PVN decreased rapidly after LPS in TR?-/- and WT mice and restored after 24h in TR?-/- mice, but not in WT. LPS increased D2 mRNA expression in the PVN region in both TR?-/- and WT mice, but the relative increase was much higher in TR?-/- mice. LPS decreased D3 mRNA expression in TR?-/- mice while no statistically significant difference was observed in WT mice. LPS increased D2 mRNA expression in the ARC of both TR?-/- and WT mice. In conclusion, basal hypothalamic thyroid hormone metabolism is not different in TR?-/- and WT mice despite alterations in basal serum thyroid hormone levels. The TR? gene is involved in LPS-induced alterations of hypothalamic D2, D3 and TRH expression in the PVN region but not in D2 induction in the ARC.