Interactions between sex steroid hormones and leptin in women.: Studies in vivo and in vitro

OBJECTIVE: To investigate the associations between sex hormones and leptin. In addition, to investigate the direct effect of sex hormones by incubations of human subcutaneous adipose tissue explants, in vitro. DESIGN: Cross-sectional study and an experimental in vitro study. SUBJECTS: 36 women (age, 23 - 65 y; body mass index, BMI, 19 - 65 kg/m(2)) participated in the cross-sectional study. Subcutaneous abdominal biopsies were taken from nine women (age, 28 - 46 y; BMI, 25.5 - 36.0 kg/m2) for the in vitro study. MEASUREMENTS: Fat distribution parameters (by dual-energy X-ray absorptiometry and anthropometry), sex hormones, leptin and insulin. RESULTS: Leptin correlated significantly with most estimates of adipose tissue mass (r = 0.5 - 0.9, P < 0.05). However, when the study group was divided in three equal groups (non-obese, obese, and very-obese) it revealed that the correlation predominantly was found in non-obese. In simple correlation analysis leptin was significantly associated with estimates of adipose tissue, insulin and several sex hormones. However, in multiple regression analysis only insulin (partial correlation coefficient = 0.55, P < 0.004) and percentage fat mass (partial correlation coefficient = 0.72, P < 0.001) were significantly and independently correlated with leptin without any independent effect of sex hormones. These findings were in agreement with the in vitro studies where neither estrogen nor androgens (testosterone or DHT) affected subcutaneous adipose tissue leptin production. Dexamethasone (10 nM) stimulated adipose tissue leptin production 3-fold (P < 0.001). CONCLUSION: In regression analysis, where both insulin and measurements of fat mass were taken into account, androgens or estrogens did not independently contribute to the variation in leptin levels. Estrogens and androgens had no direct effects on adipose tissue leptin production in vitro. Thus, the sexual dimorphism evident in serum leptin is not likely to be due to a direct influence of sex hormones on leptin production in females.