Effect of estradiol on thermoregulatory responses in ovariectomized rats administered ostruthin, a TWIK-related potassium channel agonist

This study investigated the effects of estradiol (E2) on ostruthin-induced thermoregulatory responses in ovariectomized rats, a menopausal model. Ostruthin, a component extracted from Paramignya trimera, is an agonist of cold receptors, specifically the TWIK-related potassium channels 1 (TREK1) and 2 (TREK2). Wistar rats were ovariectomized and implanted with a silastic tube with or without E2 (E2(+) and E2(−) groups). Ostruthin or vehicle was injected intraperitoneally. Body temperature (Tb), locomotor activity, tail skin temperature (Ttail), oxygen consumption, and tail-hiding behavior were measured continuously. Plasma concentrations of catecholamines, triiodothyronine, and thyroxine were measured. mRNA expression levels of TWIK-related potassium channels, transient receptor potential cation channels, E2 receptors, and selected four genes in dorsal root ganglia were assessed. For the electrophysiological study, ventral root reflex responses induced by dorsal root stimulation were measured in in vitro preparations of neonatal rat spinal cord applied 500 μM ostruthin. Ostruthin increased Tb in the E2(+) group. In ostruthin-treated groups, Tb in the E2(+) group was greater than that in the E2(−) group. Ostruthin decreased Ttail. There was a tendency for E2 to decrease Ttail. E2 increased plasma triiodothyronine. E2 increased TREK1, nerve growth factor-inducible, and nitric oxide synthase 1 mRNA level. No significant differences in other measurements were observed among the groups. The excitation of sensory nerves by ostruthin and the increase of TREK1 by E2 may facilitate cold sensitivity. Ostruthin and E2 suppressed heat dissipation by tail skin vasomotor control. E2 may increase Tb in a menopausal model, potentially through modulation of TREK1. To investigate the effects of estradiol (E2) on ostruthin-induced thermoregulatory responses in ovariectomized rats, the dorsal root ganglia in rats were analyzed by RNA-seq.