Abstract

In addition to the direct effects of thyroid hormone (TH) on peripheral organs, recent work showed metabolic effects of TH on the liver and brown adipose tissue via neural pathways originating in the hypothalamic paraventricular and ventromedial nucleus (PVN and VMH). So far, these experiments focused on short-term administration of TH. The aim of this study is to develop a technique for chronic and nucleus-specific intrahypothalamic administration of the biologically active TH tri-iodothyronine (T₃). We used beeswax pellets loaded with an amount of T₃ based on in vitro experiments showing stable T₃ release (∼5 nmol l⁻¹) for 32 days. Upon stereotactic bilateral implantation, T₃ concentrations were increased 90-fold in the PVN region and 50-fold in the VMH region after placing T₃-containing pellets in the rat PVN or VMH for 28 days respectively. Increased local T₃ concentrations were reflected by selectively increased mRNA expression of the T₃-responsive genes Dio3 and Hr in the PVN or in the VMH. After placement of T₃-containing pellets in the PVN, Tshb mRNA was significantly decreased in the pituitary, without altered Trh mRNA in the PVN region. Plasma T₃ and T₄ concentrations decreased without altered plasma TSH. We observed no changes in pituitary Tshb mRNA, plasma TSH, or plasma TH in rats after placement of T₃-containing pellets in the VMH. We developed a method to selectively and chronically deliver T₃ to specific hypothalamic nuclei. This will enable future studies on the chronic effects of intrahypothalamic T₃ on energy metabolism via the PVN or VMH.