Naringenin increases pituitary Sirt1/TSH ratio and induces ultrastructural changes in the thyroids of old-aged male Wistar rats

Abstract

Objectives: Fruit-derived polyphenols can affect pituitary thyroid stimulating hormone (TSH) secretion, which is mediated by Sirt1 protein. Recently, we have shown that citrus polyphenol naringenin (NAR) increases serum TSH level and modify thyroid structure in terms of increased hormone biosynthesis. Keeping in mind that higher serum TSH level and elevated Sirt1 expression are tightly connected with longevity, we wanted to test whetherNAR administration affects pituitary TSH and Sirt1 immunofluorescent expression and changes thyroid ultrastructure in 24-month-old male Wistar rats. Methods: NAR was administrated orally (15 mg/kg b.m.) during 4 weeks, while the control group received vehicle, sunflower oil. Quantitative analysis of labeled TSH and Sirt1 proteins in TSH cells considered the relative intensity of fluorescence (RIF) measurements, while ultrastructural analysis was performed in the thyroids. Results: Increased (p<0.05) Sirt1 RIF as well as Sirt1/TSH ratio were observed, while TSH content-reflecting RIF decreased (p<0.05), all after NAR treatment. In line with this effect of NAR, thyroids of the same group responded to direct TSH stimulation in comparison with the controls. Namely, ultrastructural analysis showed higher thyroid epithelium, well developed rough endoplasmic reticulum and polymorphic lysosomes which were more abundant than in the control group. Some lysosomes were attached to colloid droplets, unequivocally indicating the gland secretory activity. Conclusion: Citrus flavanone NAR increases pituitary Sirt1/TSH expression ratio in old rats. This corresponds with decreased thyrotrope TSH content/increased secretion, while ultrastructure of the thyroids follows direct TSH stimulation. These results, for the first time, show potency of NAR to positively interfere with TSH secretion in old-aged rats, which may contribute to the healthy aging and longevity.