Changes in Insulin, Glucose and Ketone Bodies, But Not Leptin or Body Fat Content Precede Restoration of Luteinising Hormone Secretion in Ewes

The reproductive system, including pulsatile luteinising hormone (LH) secretion, is inhibited by deficits in energy availability and restored by energy surfeits. Plasma LH, insulin, leptin, ghrelin, glucose, ketone body, and nonesterified fatty acid concentrations were measured in ovariectomised, food-restricted ewes before and after return to ad libitum feeding to determine the factors that change in time to account for the restoration of pulsatile LH secretion. At 07.00 h, blood was sampled every 10 min for 5 h from ovariectomised, hypogonadotrophic, chronically food-restricted and ad libitum-fed ewes (Fed). At 12.00 h, four of the food-restricted sheep were given ad libitum access to food (Re-Fed), while three ewes continued to be food restricted (Restricted). Sampling continued for 5 h and resumed again on the mornings of days 2, 4, and 9. A pulse of LH was seen within 1 h of re-feeding in all Re-Fed ewes, and interpulse interval (IPI) was significantly shorter in Re-Fed compared to Restricted ewes and longer than in Fed ewes during the period after re-feeding. Re-Fed LH IPI was not restored to that of Fed ewes until sometime between days 4 and 9. The first pulse occurred within minutes, whereas restoration of IPI occurred after 4-8 days. Prior to the initial LH pulses seen in Re-Fed ewes, plasma ketone bodies first fell and then rose to levels significantly above those in Restricted ewes. Significant changes in circulating insulin, ghrelin, glucose, and total ketone body concentrations, daily food intake and lean body mass preceded restoration of Re-Fed LH IPI some time between days 4 and 9, but there were no significant changes in adiposity or circulating leptin concentrations, consistent with the hypothesis that LH pulses are reinitiated by changes in the availability of oxidisable metabolic fuels and possibly insulin, but not leptin concentrations.