We investigated how ghrelin can mediate the inhibitory effects of fasting on the reproductive axis using female rats with a point mutation to the gene encoding GHSR.For this purpose, we fasted FHH GHSR KO rats and their WT counterparts starting on the evening of metestrus and ending 42h later on the expected proestrus afternoon. Rats were then euthanized; blood was collected and analyzed to compare plasma LH and estrogen concentrations between these animals and controls. Fasting significantly decreased LH concentrations in all rats regardless of their genotype. Interestingly, GHSR KO rats showed overall higher LH concentrations than WT rats regardless of their condition. Estrogen levels were not influenced by the genetic mutation and fasting. These findings suggest that ghrelin signalling is not required for a fastinginduced decrease in LH concentrations. However, ghrelin may modulate reproductive function as a negative feedback signal that reduces LH release regardless of energy state.iii