Potentiation of Epinephrine-Induced Lipolysis by Catechol Estrogens and Their Methoxy Derivatives*

The role of catechol estrogens or methoxy derivatives of these compounds in the regulation of lipolysis was evaluated using adipocytes prepared from rat epididymal fat pads. Glycerol released into the incubation medium was measured as an index of lipolysis. When adipocytes were incubated with epinephrine alone (5 X 10-7 M), glycerol formation was increased 2- to 5-fold over that in untreated cells. Incubation of cells in the presence of 2-hydroxyestrone, 2-hydroxyestradiol, 2- methoxyestrone, 2-methoxyestradiol, estrone, or 17β-estradiol did not increase triglyceride hydrolysis over that in untreated cells. However, when cells were incubated with epinephrine together with either 2-hydroxyestrone, 2-hydroxyestradiol, or 2- methoxyestradiol, glycerol formation was increased 2- to 3-fold over the rate in cells treated with epinephrine alone. Estrone, 17β-estradiol, and 2-methoxyestrone did not affect the rate of epinephrine-induced lipolysis in adipocytes. To define whether catechol estrgens were potentiating the lipolytic effect of epinephrine by competition for catechol-O-methyltransferase (COMT), adipocytes were incubated with epinephrifre in the presence of a number of COMT inhibitors. Each of these COMT inhibitors potentiated the lipolytic effect of epinephrine, but did not potentiate further the stimulatory effect of catechol estrogens on epinephrine-induced lipolysis. 2-Hydroxyestrone, 2-hydroxyestradiol, or 2-methoxyestradiol did not poterttiate the lipolytic effect of soterenol, a β-adrenergic agonist that is not a substrate for COMT. The steroids that potentiated the epinephrine- induced lipolytic response also inhibited the formation of 3Hmetanephrine from 3Hepinephrine in rat adipocytes. These data suggest that catechol estrogens compete with epinephrine for binding to COMT and thereby enhance the lipolytic effect of epinephrine.