LEPTIN INDIRECTLY AFFECTS ESTROUS CYCLES BY INCREASING METABOLIC FUELOXIDATION

In previous experiments, lean Syrian hamsters fasted on days 1 and 2 o f the estrous cycle failed to show sex behavior and ovulation normally expected to occur on the evening of day 4. The first goal of the pres ent experiment was to determine whether systemic treatment with the ob (obese) protein leptin could reverse the effects of fasting on estrou s cyclicity, social behaviors, and ovulation rate. Fasting-induced ane strus was reversed and normal sex and social behavior and ovulation ra te were restored in hamsters injected intraperitoneally with 5 mg/kg l eptin every 12 h during fasting on days 1 and 2 of the estrous cycle. A second goal was to test whether the effects of leptin could be preve nted by treatment with pharmacological agents that block the oxidation of metabolic fuels. Glucose oxidation was blocked by treatment with 2 -deoxy-D-glucose (2DG) and fatty acid oxidation was blocked by treatme nt with methyl palmoxirate (MP). 2DG (1000 mg/kg) or MP (20 mg/kg) was administered at doses that did not induce anestrus in hamsters fed ad libitum. As in the first experiment, fasting-induced anestrus was rev ersed by leptin treatment. However, when each injection of leptin was preceded by an injection of 2DG or MP, leptin treatment did not revers e fasting-induced anestrus. In summary, metrous cyclicity was not rest ored when oxidation of metabolic fuels was blocked, despite high endog enous levels of leptin. These results are consistent with the hypothes is that leptin acts indirectly on the reproductive system by increasin g fuel oxidation. (C) 1998 Academic Press.