Abstract
Thyrotropin-releasing hormone (TRH) plays several roles as a hormone/neuropeptide. Diencephalic TRH (dTRH) participates in the regulation of blood pressure in diverse animal models, independently of the thyroid status. The present study aimed to evaluate whether chronic overexpression of TRH in mice affects cardiovascular and metabolic variables. We developed a transgenic (TG) mouse model that overexpresses dTrh. Despite having higher food consumption and water intake, TG mice showed significantly lower body weight respect to controls. Also, TG mice presented higher blood pressure, heart rate, and locomotor activity independently of thyroid hormone levels. These results and the higher urine noradrenaline excretion observed in TG mice suggest a higher metabolic rate mediated by sympathetic overflow. Cardiovascular changes were impeded by siRNA inhibition of the diencephalic Trh overexpression. Also, the silencing of dTRH in the TG mice normalized urine noradrenaline excretion, supporting the view that the cardiovascular effects of TRH involve the sympathetic system. Overall, we show that congenital dTrh overexpression leads to an increase in blood pressure accompanied by changes in body weight and food consumption mediated by a higher sympathetic overflow. These results provide new evidence confirming the participation of TRH in cardiovascular and body weight regulation.
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Acknowledgments
We are grateful to Dr. R. Ariel Gomez (Department of Pediatrics and Department of Biology, University of Virginia, Charlottesville, VA, USA) and his group for the development of the transgenic mice. We also thank Noelia Gonzales Mansilla for the technical assistance.
Funding
This work was supported by PICT 2010-2581 and PICT 2018-00620 (Agencia Nacional de Promoción Científica y Tecnológica). Young investigator fellowship from the Argentine Society of Hypertension (SAHA), Buenos Aires, Argentina.
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Conception and design of research were performed by Carlos J. Pirola. Experiments were performed by María Silvina Landa, Silvia I Garcia, Ludmila Peres Diaz, Mariano Schuman, and Maia Aisicovich. Data analysis was performed by María Silvina Landa and Silvia I. García. Interpreted experimental results were performed by María Silvina Landa, Silvia I. García, Carlos J. Pirola, and Mariano L. Schuman. Carlos J. Pirola and Silvia García drafted, edited, and revised the final version of the manuscript. All authors read and approved the final manuscript.
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The experimental procedures and protocols were approved by the Institutional Animal Care and Use Committee CICUAL, Instituto de Investigaciones Médicas, IDIM-CONICET (N°034-15).
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Key Points
• Transgenic mice overexpressing TRH present higher blood pressure and a lower body weight despite increased food consumption and water intake.
• A specific siRNA against Trh injected intracerebroventricularly normalized blood pressure.
• Cardiovascular and body weight regulation changes induced by TRH overexpression are dependent on an increased sympathetic tone but not thyroid hormones.
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Landa, M.S., García, S.I., Schuman, M.L. et al. Cardiovascular and body weight regulation changes in transgenic mice overexpressing thyrotropin-releasing hormone (TRH). J Physiol Biochem 76, 599–608 (2020). https://doi.org/10.1007/s13105-020-00765-x
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DOI: https://doi.org/10.1007/s13105-020-00765-x