Resource availability, and therefore nutritive condition, is one of the most important factors affecting the growth and developmental trajectories of animals in their early life stages. However little is understood about the mechanisms that link nutritive condition to growth  and developmental processes at the physiological level, especially during the earliest phases of the larval or fetal stage, although we know that nutritional state is associated with the timing of important life history transitions such as metamorphosis, birth or puberty. Because the neuroendocrine stress axis is a major physiological system known to affect the timing of metamorphosis in amphibians, we propose that nutritional cues may modulate timing of metamorphosis via interactions of physiological energy balance indicators with the stress axis. To address this assertion, we examined the interactions between the stress axis and two presumptive energy balance indicators, neuropeptide Y (NPY), a potential indicator of proximate levels of food intake,  and leptin, a peptide hormone thought to be secreted by fat and may indicate long-term nutritional condition, within the context of metamorphic timing in amphibians.
Results/Conclusions

We conducted several laboratory experiments to show that both NPY and leptin are energy balance indicators in amphibians that modulate food intake and interact with growth, development, and immune systems during the tadpole stage. We showed that NPY gene expression in the tadpole brain increases as metamorphosis approaches, suggesting that NPY is related to the increase in stress hormones that peak upon metamorphic climax. To determine how leptin may interact with the stress axis in modulating metamorphic timing we conducted a mesocosm experiment in which late-staged woodfrog tadpoles were fed and injected (ip) with saline, food deprived for 5 days and injected with saline, or food deprived and injected with leptin during the 5 days of restriction. We found that food-restricted tadpoles metamorphosed sooner than fed tadpoles, as shown in many previous studies (i.e., stress-induced metamorphosis), and food-restricted tadpoles injected with leptin had higher survival, lost less weight, and began to metamorphose earlier than food-restricted tadpoles injected with saline. Given that leptin expression varies with nutritive condition in tadpoles, this experiment suggests that leptin may be physiological indicator of nutritive condition that mediates condition-dependent developmental responses to environmental stressors. We propose that these factors interact to fine-tune the timing of major life history transitions according to nutritional state and stress level in vertebrates.