Central Thyrotropin-Releasing Hormone Infusion Opposes Cardiovascular and Metabolic Suppression during Caloric Restriction

Abstract

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) or saline (0.25 µl/h) for 7 days via osmotic pump. This dose of TRH did not significantly alter peripheral free T₄ 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.

Knocking down the diencephalic thyrotropin-releasing hormone precursor gene normalizes obesity-induced hypertension in the rat

“…Furthermore, we (8,12) have consistently found that diencephalic TRH manipulation does not necessarily change thyroid status. This have been confirmed by other groups in different settings (23).…”

“…Accordingly, in our hands, TRH AS treatment was effective and selective in decreasing the elevated concentrations of NMN and MN of obese animals, which added additional evidence to the existence of a TRH-dependent elevation of ABP mediated by sympathetic overflow. Interestingly, prepro-TRH siRNA treatment induced a significant increase in body weight, indicating that diencephalic TRH serves as a negative modulator of body weight gain, probably by acting on energy balance (21,23,24).…”

Thyroid hormone is required for hypothalamic neurons regulating cardiovascular functions

“…Thyrotropin-releasing hormone (TRH), known to have central effects on the control of the autonomic nervous system (23)(24)(25), excited 48% ( Figure 3D) and inhibited 19% of the neurons. Some of these inhibitions were associated with an increase in inhibitory postsynaptic potentials (Supplemental Figure 2, F and G), suggesting that the AHA pv + neurons are part of a TRH excited inhibitory network.…”

Association between diencephalic thyroliberin and arterial blood pressure in agouti-yellow and ob/ob mice may be mediated by leptin

“…Basing our conclusions on the knowledge that cardiovascular effects of dTRH are mediated by the sympathetic system [24,25], we propose that the leptin-induced sympathetic tone may be mediated by a dTRH increase. In fact, these results are in agreement with those that we found in an obese rat model induced by a high-fat diet in which the elevation of body weight is accompanied by hyperleptinemia, dTRH elevation, and hypertension with elevation of the sympathetic tone.…”