Central administration of thyrotropin releasing hormone (TRH) and related peptides inhibits feeding behavior in the Siberian hamster

Steward, C. A.; Horan, Tracey L; Schuhler, Sandrine; Bennett, Gerald; Ebling, Francis J. P.

doi:10.1097/00001756-200304150-00006

Cited by 39 publications

(33 citation statements)

References 21 publications

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“…This is believed to be similar to the condition of "sick euthyroid" seen in critically ill patients (43). It has also been shown that centrally acting TRH, independent of endocrine action, regulates several metabolic and behavioral parameters in rats and Siberian hamsters, including food intake and locomotor activity (44,45).…”

Section: Introductionmentioning

confidence: 70%

Regulation of hypothalamic prohormone convertases 1 and 2 and effects on processing of prothyrotropin-releasing hormone

Sanchez¹,

Goldstein²,

Stuart³

et al. 2004

J. Clin. Invest.

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Regulation of energy balance by leptin involves regulation of several neuropeptides, including thyrotropinreleasing hormone (TRH).Synthesized from a larger inactive precursor, its maturation requires proteolytic cleavage by prohormone convertases 1 and 2 (PC1 and PC2). Since this maturation in response to leptin requires prohormone processing, we hypothesized that leptin might regulate hypothalamic PC1 and PC2 expression, ultimately leading to coordinated processing of prohormones into mature peptides. Using hypothalamic neurons, we found that leptin stimulated PC1 and PC2 mRNA and protein expression and also increased PC1 and PC2 promoter activities in transfected 293T cells. Starvation of rats, leading to low serum leptin levels, decreased PC1 and PC2 gene and protein expression in the paraventricular nucleus (PVN) of the hypothalamus. Exogenous administration of leptin to fasted animals restored PC1 levels in the median eminence (ME) and the PVN to approximately the level found in fed control animals. Consistent with this regulation of PCs in the PVN, concentrations of TRH in the PVN and ME were substantially reduced in the fasted animals relative to the fed animals, and leptin reversed this decrease. Further analysis showed that proteolytic cleavage of pro-thyrotropin-releasing hormone (proTRH) at known PC cleavage sites was reduced by fasting and increased in animals given leptin. Combined, these findings suggest that leptin-dependent stimulation of hypothalamic TRH expression involves both activation of trh transcription and stimulation of PC1 and PC2 expression, which lead to enhanced processing of proTRH into mature TRH.

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Section: Introductionmentioning

confidence: 70%

Regulation of hypothalamic prohormone convertases 1 and 2 and effects on processing of prothyrotropin-releasing hormone

Sanchez¹,

Goldstein²,

Stuart³

et al. 2004

J. Clin. Invest.

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“…These findings are generally consistent with previous reports of acute or chronic TRH administration. Indeed, central TRH infusion has been reported to reduce food intake [20, 21], increase energy expenditure [17, 18], and increase HR and blood pressure [14, 16, 22]. …”

Section: Discussionmentioning

confidence: 99%

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

Knight¹,

Swoap

Parsons

et al. 2006

Neuroendocrinology

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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.

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“…Moreover, food deprivation inhibits TRH mRNA expression in the PVN (Fekete et al 2000). Central administration of TRH decreases food intake independent of its actions on thyroid function (Choi et al 2002, Steward et al 2003, Schuhler et al 2007. Taken together, these findings suggest that CRH and TRH neurons may be effector neurons of Quantitative data indicate that (B) AAV-MC4R-shRNA-EGFP significantly reduces the level of MC4R mRNA expression in the PVN, but exhibits (C) no significant effects on aVP mRNA expression in the PVN.…”

Section: Discussionmentioning

confidence: 85%

Adeno-associated virus-mediated knockdown of melanocortin-4 receptor in the paraventricular nucleus of the hypothalamus promotes high-fat diet-induced hyperphagia and obesity

Garza

Kim

Liu

et al. 2008

Journal of Endocrinology

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Pharmacological and genetic studies have suggested that melanocortin-4 receptor (MC4R) signaling in the paraventricular nucleus of hypothalamus (PVN) regulates appetite and energy balance. However, the specific role of MC4R signaling in PVN neurons in these processes remains to be further elucidated in normally developed animals. In the present study, we employed RNA interference to determine whether MC4R knockdown in the PVN modulates food intake and body weight in adult rats. Adeno-associated viral (AAV) vectors encoding short hairpin RNAs targeting MC4R (AAV-shRNA-MC4R) were generated to induce MC4R knockdown in the PVN. By in situ hybridization, we detected a high-level expression of Dicer, a key enzyme required for shRNA-mediated gene silencing, along the entire rostrocaudal extent of the PVN. Bilateral injection of AAV-shRNA-MC4R vectors into the PVN of the adult rat resulted in significant and specific reduction of MC4R mRNA expression. Animals with MC4R knockdown exhibited an increase in food intake and excessive body weight gain when exposed to a high-fat diet. Our results provide evidence that AAV-mediated silencing of MC4R on PVN neurons promotes hyperphagia and obesity in response to the dietary challenge in the adult animal.

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Central administration of thyrotropin releasing hormone (TRH) and related peptides inhibits feeding behavior in the Siberian hamster

Cited by 39 publications

References 21 publications

Regulation of hypothalamic prohormone convertases 1 and 2 and effects on processing of prothyrotropin-releasing hormone

Regulation of hypothalamic prohormone convertases 1 and 2 and effects on processing of prothyrotropin-releasing hormone

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

Adeno-associated virus-mediated knockdown of melanocortin-4 receptor in the paraventricular nucleus of the hypothalamus promotes high-fat diet-induced hyperphagia and obesity

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