The effect of third-generation aromatase inhibitors on aromatase avtivity in visceral adipose tissue

摘要

Pathogenesis and clinical manifestations of metabolic syndrome (and other conditions characterized by the growth of fat mass and decreased adiponectin content) is associated with an imbalance of sex hormones, which develops under the influence of increased aromatase activity in adipose tissue. Drugs of the aromatase inhibitors therapeutic group are able to suppress the course of the aromatase reaction in the central and peripheral organs and tissues. The aim of our study was to establish the relationship between levels of serum adiponectin and adipose tissue aromatase avtivity in Syrian hamsters of different ages and gender with experimental metabolic syndrome and study the effect of aromatase inhibitors on these indicators. Experimental metabolic syndrome in animals was induced by a high-fat and fructose diet. The drugs were administered during the 21-st day in doses of 3.086 (exemestane), 0.309 (letrozole) and 0.126 mg/kg (anastrozole). The aromatase activity of the visceral adipose tissue was determined by the modified kinetic method based on the amount of the reaction product estradiol converted from testosterone. The content of estradiol in adipose tissue homogenate and serum adiponectin levels were measured by the immune enzyme method. The results showed a high inverse correlation between serum adiponectin and adipose tissue aromatase activity in hamsters. Aromatase inhibitors caused a decrease in the adipose tissue aromatase activity and increase in serum adiponectin levels. Letrazol demonstrated the greatest effect, it reduced aromatase activity in adipose tissue by 72–84% and increased serum adiponectin content by 1.6–1.8 times. At the same time, intra-group correlation of the studied parameters was significant. The results show the relationship between adiponectin level and adipose tissue aromatase activity and ability to change these rates by the way of aromatase inhibitors, which may be useful in clinical practice. Third-generation aromatase inhibitors are promising drugs for metabolic syndrome treatment and require further study in clinical trials.