Leptin Regulates Hypothalamus-Pituitary-Thyroid Axis via TRH in Energy Expenditure During Fasting: The Study on TRH Deficient Mouse

Abstract Objectives: The hypothalamic-pituitary-thyroid (HPT) axis plays a significant role in the regulation of energy expenditure. Previous reports demonstrated that thyroid hormones are critically involved metabolic process, and hypothyroidism was induced by fasting. mechanism which TRH neurons sense alterations peripheral stores is supposed to be regulated leptin, an adipose tissue-derived hormone. Leptin initially considered as hormone prevent obesity, it later showed major leptin signal switch from fed starved state at hypothalamic level. Recently, we generated TRH-deficient mice (TRH-/-). exhibit tertiary/central with characteristic elevation serum TSH level diminished biological activity. In this study, used TRH-/- investigate physiological fasting expenditure, including leptin. Methods: Twelve-week-old male F2 hybrid ICR were study. (1) Wild-type (WT) fasted up 50 hrs. Blood samples collected tail veins various points. Anterior pituitary obtained euthanized before after 16 hrs (2) Serum free T4 (FT4) levels assessed. (3) expression TSHβ mRNA anterior detected using qPCR assays. (4) We repeated these experiments administration; (0.5μg/g•BW) administrated every 6 hours starting 2 Results: WT, FT4 decreased chronologically during approximately 50% 70% also 30% compared Administration recovered basal However, not levels. By contrast, TRH-/-, indicating decrease independent TRH. suggesting recovery dependent. 75% fasting, no administration observed same WT. about WT It did correlate addition, increase TRH-/-. These findings suggested completely TRH-dependent Conclusion: Fasting-induced hypothyroxinemia regulates H-P-T via fasting-induced may modulate activity TSHβ.