The role of estradiol in mediating leptin's effects on body weight was asse
ssed in ovariectomized (OVX) mice before and after the onset of obesity. Ov
ariectomy did not alter leptin levels before the onset of obesity, and estr
adiol adminstration (0.05-17 mu g/day for 14 days) did not significantly al
ter leptin levels if they were corrected for the estradiol-induced reductio
n in body fat. The converse was also true, in that leptin administration (0
.4-140 mu g/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 o
f leptin's effect on fat mass reduction when it was given in combination wi
th leptin to lean intact or OVX mice. Estradiol may have indirectly affecte
d 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. Take
n together, these data suggested that I) estradiol does not directly regula
te leptin secretion or its effects on fat mass and 2) leptin does not direc
tly regulate estradiol secretion or its effects on fat mass. Leptin and est
radiol, however, may interact in an indirect fashion to affect fat utilizat
ion.