Does estradiol mediate leptin's effects on adiposity and body weight?

The role of estradiol in mediating leptin's effects on body weight was assessed in ovariectomized (OVX) mice before and after the onset of obesity. Ovariectomy did not alter leptin levels before the onset of obesity, and estradiol adminstration (0.05-17 μg/day for 14 days) did not significantly alter leptin levels if they were corrected for the estradiol-induced reduction in body fat. The converse was also true, in that leptin administration (0.4-140 μg/day) did not alter estradiol levels in intact mice. Furthermore, neither estradiol reduction (via ovariectomy) nor addition (via exogenous administration) significantly altered leptin's ability to reduce fat mass. Leptin was equally effective in reducing body weight in lean or obese OVX mice and intact controls. Finally, estradiol did not change the magnitude of leptin's effect on fat mass reduction when it was given in combination with leptin to lean intact or OVX mice. Estradiol may have indirectly affected leptin efficacy, because leptin did not produce as large a change in fat mass at lower doses in lean OVX mice as it did in intact counterparts. Taken together, these data suggested that 1) estradiol does not directly regulate leptin secretion or its effects on fat mass and 2) leptin does not directly regulate estradiol secretion or its effects on fat mass. Leptin and estradiol, however, may interact in an indirect fashion to affect fat utilization.