leptin and methyl-2-tetradecylglycidate

A 48-h period of fasting inhibits estrous cycles in Syrian hamsters, and fasting-induced anestrus can be prevented by intracerebroventricular treatment with leptin during the fasting period. In the present experiment, the effects of intracerebroventricular leptin were blocked by systemic treatment with inhibitors of metabolic fuel oxidation. Leptin was infused continuously into the lateral ventricles (1 microgram/day) during fasting on days 1 and 2 of the estrous cycle. Intraperitoneal injection of 2-deoxy-D-glucose (2DG) was used to block both central and peripheral glucose oxidation, and intragastric treatment with methyl palmoxirate (MP) was used to inhibit peripheral long-chain fatty acid oxidation during the fasting and leptin-treatment period. 2DG or MP were administered at doses that did not induce anestrus in ad libitum-fed hamsters. Despite elevated central levels of leptin, fasting-induced anestrus occurred in hamsters treated with either 2DG or MP. Thus an elevated intracerebroventricular leptin concentration is not a sufficient condition for normal estrous cycles when fuel oxidation is inhibited. These results raise the possibility that central leptin influences reproduction by indirect effects on peripheral fuel metabolism.

Topics: Anestrus; Animals; Brain; Cricetinae; Deoxyglucose; Energy Metabolism; Epoxy Compounds; Estrus; Fasting; Fatty Acids; Female; Injections, Intraventricular; Leptin; Mesocricetus; Oxidation-Reduction; Propionates

In previous experiments, lean Syrian hamsters fasted on days 1 and 2 of 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 present experiment was to determine whether systemic treatment with the ob (obese) protein leptin could reverse the effects of fasting on estrous cyclicity, social behaviors, and ovulation rate. Fasting-induced anestrus was reversed and normal sex and social behavior and ovulation rate were restored in hamsters injected intraperitoneally with 5 mg/kg leptin 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 prevented 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 treatment 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 reversed by leptin treatment. However, when each injection of leptin was preceded by an injection of 2DG or MP, leptin treatment did not reverse fasting-induced anestrus. In summary, estrous cyclicity was not restored when oxidation of metabolic fuels was blocked, despite high endogenous levels of leptin. These results are consistent with the hypothesis that leptin acts indirectly on the reproductive system by increasing fuel oxidation.

Topics: Aggression; Animals; Antimetabolites; Cricetinae; Deoxyglucose; Energy Metabolism; Epoxy Compounds; Estrus; Fasting; Female; Hypoglycemic Agents; Leptin; Mesocricetus; Ovulation; Oxidation-Reduction; Posture; Propionates; Proteins; Sexual Behavior, Animal; Vagina