Central thyrotropin-releasing hormone infusion opposes cardiovascular and metabolic suppression during caloric restriction

Inhibition of hypothalamic thyrotropin-releasing hormone (TRH) neuronal activity is a well-established adaptation to caloric restriction (CR) that suppresses pituitary secretion of thyroid-stimulating hormone, but may also participate in modulation of autonomic function. Thus, we hypothesized that decreased hypothalamic TRH activity contributes to CR-induced bradycardia and decreased metabolic rate. To test this hypothesis, male Sprague-Dawley rats were instrumented with telemetry devices for measurement of heart rate (HR) and blood pressure (BP) and a lateral intracerebroventricular (i.c.v.) guide cannula for central infusions. After recovery, rats were housed in metabolic chambers and given either ad libitum (ad-lib) or CR treatments for 7 days; half of each diet group was then given continuous i.c.v. infusions of TRH (25 nmol/h) orsaline(0.25 mu l/h) for 7 days via osmotic pump. This dose of TRH did not significantly alter peripheral free T-4 levels. In ad-lib rats, TRH infusion produced small reductions in food intake and small increases in HR and BP over saline-infused controls. In CR rats, TRH infusion resulted in an increase in HR and also energy expenditure over saline-infused controls. These results support the hypothesis that suppression of central TRH activity contributes to the homeostatic suppression of energy expenditure and HR observed during CR. Copyright (c) 2006 S. Karger AG, Basel.