The influence of equol on the hypothalamic-pituitary-thyroid axis and hepatic lipid metabolic parameters in adult male rats

Abstract

Aims: Equol, the principal active metabolite of soy-derived phytoestrogen daidzein, has well-known estrogenic actions. Results of several studies indicate that equol may also have anti-androgenic activities. However, mechanisms of action of equol on hypothalamic-pituitary-thyroid axis (HPTA) and hepatic lipid metabolism in adult male rats have not been determined yet. Main methods: Equol at two doses of 100 and 250 mg/kg body weight (BW)/day was orally gavaged for 5 days to groups of 4-month-old male rats. As a positive anti-androgenic control group, animals received 100 mg of pure anti-androgenic drug flutamide/kg BW/day. Circulating concentrations of thyroid hormones and lipids, and expression levels of genes underlying HPTA function were determined by radioimmunoassay and TaqMan (R) real-time reverse transcription polymerase chain reaction, respectively. Key findings: Flutamide significantly decreased relative prostate weight, whereas equol did not. Both equol and flutamide caused a significant increase in relative liver weights, and decreases in plasma levels of total tetraiodothyronine (T4) and triiodothyronine (T3), whereas free T4 and T3 concentrations were not reduced. Equol caused the marked down-regulation of hypothalamic thyrotropin-releasing hormone mRNA expression, whereas flutamide did not. Equol as well as flutamide significantly down-regulated the expression levels of pituitary thyrotropin beta-subunit mRNA, without altering thyrotropin secretion. Equol caused reductions in plasma levels of total cholesterol, high- and low-density lipoproteins and triglycerides, whereas flutamide exerted opposite effects. Significance: This is the first study to reveal that in male rats equol did not affect HPTA function and liver lipid metabolism through the anti-androgenic pathway, however, the intrinsic estrogenic actions of equol were observed. (C) 2015 Elsevier Inc. All rights reserved.