Endocrine regulation of regeneration: Linking global signals to local processes

Regeneration in amphibians and reptiles has been explored since the early 18th century, giving us a working in vivo model to study epimorphic regeneration in vertebrates. Studies aiming to uncover primary mechanisms of regeneration have predominantly focused on genetic pathways regulating specific stages of the regeneration process: wound healing, blastema formation and growth, and pattern formation. However, studies across organisms show that environmental conditions and physiological state of the animal can affect the rate or quality of regeneration, and endocrine signals are likely the mediators of these effects. Endocrine signals working/acting directly on receptors expressed in the structure or via neuroendocrine pathways can affect regeneration by modulating immune response to injury, allocation of energetic resources, or by enhancing or inhibiting proliferation and differentiation pathways in regenerating tissue. This review discusses the cumulative knowledge known about endocrine regulation of regeneration and important future research directions of interest to both ecological and biomedical research.