Cardiovascular and body weight regulation changes in transgenic mice overexpressing thyrotropin-releasing hormone (TRH)

LANDA, MARÍA SILVINA; GARCÍA, SILVIA INÉS; SCHUMAN, MARIANO LUIS; PERES DIAZ, LUDMILA SOLEDAD; AISICOVICH, MAIA; PIROLA, CARLOS JOSÉ

JOURNAL OF PHYSIOLOGY AND BIOCHEMISTRY

SERVICIO PUBLICACIONES UNIVERSIDAD NAVARRA

Año: 2020

1138-7548

Thyrotropin-releasinghormone(TRH)plays several rolessa hormone/neuropeptide. DiencephalicTRH(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 activityindependently of thyroid hormone levels. Theseresults and the higher urine noradrenaline excretion observed inTG micesuggest a highermetabolic ratemediatedbysympathetic overflow.Cardiovascularchanges were impeded bysiRNA 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.