BACKGROUND: Cold exposure increases thyrotropin-releasing hormone (TRH) expression primarily in the hypothalamic paraventricular nucleus (PVN). The PVN is a well-known hypothalamic hub in the control of energy metabolism. TRH terminals and receptors are found on PVN neurons. We hypothesized that TRH release in the PVN plays an important role in the control of thermogenesis and energy mobilization during cold exposure. <br><br>Methods: Male Wistar rats were exposed to a cold environment (4oC) or TRH retrodialysis in the PVN for 2-hours. We compared the effects of cold exposure and TRH administration in the PVN on plasma glucose, corticosterone and thyroid hormone concentrations, body temperature, locomotor activity as well as metabolic gene expression in liver and brown adipose tissue. <br><br>Results: Cold exposure increased body temperature, locomotor activity and plasma corticosterone concentrations, but blood glucose concentrations were similar to that of room temperature control animals. TRH administration in the PVN also promptly increased body temperature, locomotor activity and plasma corticosterone concentrations. However, TRH administration in the PVN markedly increased blood glucose concentrations and endogenous glucose production (EGP) compared to saline controls. Selective hepatic sympathetic or parasympathetic denervation reduced the TRH-induced increase in glucose concentrations and EGP. Gene expression data indicated increased gluconeogenesis in liver and lipolysis in brown adipose tissue, both after cold exposure and TRH administration. <br><br>Conclusions: We conclude that TRH administration in the rat PVN largely mimics the metabolic and behavioral changes induced by cold exposure indicating a potential link between TRH release in the PVN and cold defense. <br><br>.