Influence of Sex Hormones on Adiponectin Expression in Human Adipocytes

Adiponectin is an adipokine with profound antidiabetic and antiatherogenic effects. Circulating adiponectin concentrations are higher in women than in men. In order to study the molecular aspects of this sex-specific dimorphism, we examined the expression of adiponectin in human fat cells under the influence of sex hormones, using SGBS cells as an in vitro model. Androgen and estradiol receptor 1 and 2 (AR, ESR1, ESR2) mRNA expression increased dramatically during adipogenic differentiation. Stimulation with human male and female serum led to a downregulation of adiponectin expression, with male serum exerting significantly stronger inhibitory properties than female serum (p<0.05). Increasing concentrations of testosterone or estradiol influenced neither adiponectin mRNA expression and secretion nor intracellular protein expression of high-, middle-, and low-molecular-weight (HMW, MMW, LMW) adiponectin multimers. These data have been verified in in vitro-differentiated primary human adipocytes. We conclude that although human adipocytes express AR, ESR1, and ESR2 and respond to testosterone treatment with a decrease in leptin expression, expression and secretion of adiponectin is unaffected by sex steroids. We hypothesize, therefore, the existence of a serum factor that is differently regulated by sex steroids and Subsequently causes the sex dimorphism in circulating adiponectin levels.