Normalization of circulating leptin levels by fasting improves the reproductive function in obese OLETF female rats

In order to examine a possible detrimental effect of hyperleptinemia on the reproductive system, we examined whether a decrease in circulating leptin levels by fasting affects the estradiol/progesterone-induced luteinizing ho rmone (LH) and prolactin (PRL) surges in genetically obese OLETF (Otsuka-Lo ng-Evans-Tokushima-Fatty) rats. Experiments were performed on both normally fed and 3-day starved groups from ovariectomized OLETF rats and their cont rols LETO (Long-Evans-Tokushima-Otsuka). Starved LETO rats, whose leptin le vels were less than 0.5 ng/ml, did not show a significant surge of either L H or PRL. Normally fed OLETF rats, whose leptin levels were 9.7 +/- 1.8 ng/ ml, showed a significant but small surge for both LH and PRL. Interestingly , starved OLETF rats, whose leptin levels (4.1 +/- 0.7 ng/ml) were similar to those in normally fed LETO rats (3.3 +/- 0.4ng/ml), had significantly gr eater surges of both hormones than normally fed OLETF group. This study dem onstrates for the first time that the normalization of circulating leptin l evels in female OLETF rats augments the steroid-induced LH and PRL surges, and also suggests a deleterious effect of hyperleptinemia on the reproducti ve axis. (C) 2001 Harcourt Publishers Ltd.