Estradiol enhances thermoregulation induced by ostruthin, a TREK channel agonist, in ovariectomized rats

Menopausal women frequently report contradictory thermoregulatory symptoms (hot flashes and chills), believed to result from declining estradiol (E₂) levels; however, mechanisms remain unclear. TWIK-related (TREK) potassium channels function as cold receptors. Although E₂ enhances TREK1 activity in vitro, its effect on TREK-mediated thermoregulation has not been investigated in vivo. This study investigated whether E₂ facilitated TREK-mediated thermoregulation in ovariectomized rats using ostruthin, a TREK agonist. Rats were ovariectomized and implanted with silastic tubes with or without E₂, followed by ostruthin or vehicle injection. We measured thermoregulatory parameters, plasma hormones (triiodothyronine and thyroxine), and mRNA expression of cold receptors in dorsal root ganglia. Ventral root responses were examined in vitro. Ostruthin increased body temperature in E₂(+) versus E₂(-) groups, with increased triiodothyronine and upregulation of Trek1, Vgf, and Nos1. Ostruthin enhanced ventral root responses. These findings demonstrate that E₂ potentiates TREK-mediated thermoregulation through enhanced cold sensing, providing insights into menopausal disorders.