Sex and thyroid hormones are among the factors modulating energy metabolism through regulation of mitochondrial oxidative capacity. Brown adipose tissue (BAT) in old female rats has been shown to maintain, better than males, the ability to produce heat when exposed to cold. Considering the decline that takes place in gonadal and thyroid function during aging, the aim of this work was to test whether the age-related hormonal status may be a potential mediator of the gender differences in BAT decline. COX activity, UCP1, mitochondrial respiration rate, mitochondrial DNA (mtDNA), levels of mitochondrial transcription factor A (TFAM), as well as the serum levels of sex steroids (17β-estradiol, progesterone and testosterone) and thyroid hormones (T3 and T4) were measured in 6-, 18-, and 24-month (mo) old male and female rats kept at 22 °C. Six mo-old female rats showed higher thermogenic features than males. Male rats at 18-mo showed a decrease in uncoupling activity compared to females. Both genders showed marked signs of atrophy in BAT of 24-mo-old rats, characterized by a decrease in total DNA, mitochondrial protein, COX and UCP1, whereas mtDNA was found to increase. Sex steroid hormones were well correlated with BAT parameters when both genders were considered, however, T3 was the hormone with the strongest positive correlations in female rats. In conclusion, our findings provide evidence suggesting that T3 may be a potential mediator of the sexual dimorphism in the effect of aging on the functional decline of BAT.

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