Evidence that physiological levels of circulating leptin exert a stimulatory effect on luteinizing hormone and prolactin surges in rats

Increasing evidence suggests-that leptin, an adipocyte-derived hormone, may positively regulate the reproductive axis, and serve as a critical metabol ic signal linking nutrition and the reproductive function. However, along t his line there remains an as-of-yet unresolved important issue whether phys iological levels of circulating leptin exert a stimulatory effect on the re productive axis. It is also unknown whether hyperleptinemia affects the rep roductive function. In this study, we attempted to examine these unexplored issues, employing as an indicator the estradiol/progesterone-induced lutei nizing hormone (LH) and prolactin (PRL) surges in ovariectomized female rat s. Experiments were performed on normally fed, 3-day starved, 3-day starved + murine leptin (100 mu g/kg/day), and normally fed + murine leptin (300 m u g/kg/day) groups. Leptin was administered utilizing osmotic minipumps dur ing 3 days immediately before experimentation. From 11:00 to 18:00 h, blood was collected every 30 min to measure LH and PRL. The 3-day starvation com pletely abolished both LH and PRL surges, but 3-day starved + leptin (100 m u g/kg/day) group, whose plasma leptin levels (3.7 +/- 0.4 ng/ml) were simi lar to those in normally fed group (3.4 +/- 0.5 ng/ml), showed a significan t recovery of the hormonal surges. On the other hand, the magnitudes of LH and PRL surges in normally fed + leptin (300 mu g/kg/day) group, whose lept in levels were 10.8 +/- 1.5 ng/ml, were statistically the same as those-in normally fed group. These results indicate for the first time that physiolo gical concentrations of circulating leptin exert a stimulatory effect on th e steroid-induced LH and PRL surges in the rat. It was also suggested that mild hyperleptinemia of 3 days' duration may not significantly affect the h ormonal surges, (C) 1999 Academic Press.