Endocrine and enzymatic control of teleost osmoregulation: insights into physiological adaptations

Teleost fishes inhabit environments that differ markedly in salinity and ionic composition and therefore require highly coordinated mechanisms to maintain water, electrolyte, and acid-base homeostasis. Osmoregulation integrates the functions of the gills, gastrointestinal tract, kidney, and endocrine system, with ion-transporting enzymes and membrane proteins serving as major molecular effectors. This review synthesizes current knowledge of endocrine and enzymatic regulation of teleost osmoregulation, with particular emphasis on the renal mechanisms that provide a framework for renal pharmacology and translational research. In freshwater, teleosts actively acquire ions and eliminate excess water through the production of dilute urine, whereas seawater teleosts drink seawater, absorb water and ions through the gastrointestinal tract, and actively excrete excess ions through the gills while producing relatively small volumes of urine. Hormones including prolactin, cortisol, growth hormone, thyroid hormones, and stanniocalcin coordinate these responses through effects on ionocytes, renal transport processes, and epithelial permeability. Na + /K + -ATPase and other ion-transport systems provide the energetic and electrochemical basis for osmoregulation, whereas aquaporins (AQPs) contribute to regulated renal water transport. Importantly, teleost kidneys exhibit a remarkable capacity for repair and de novo nephron formation following injury, providing a valuable experimental model for investigating nephrotoxicity and renal regeneration. Pharmacological studies using established nephrotoxicants such as gentamicin and cisplatin demonstrate the utility of zebrafish for evaluating drug-induced renal injury. However, direct pharmacological manipulation of specific renal AQPs remains comparatively underdeveloped, and species-specific differences limit direct extrapolation to humans. We therefore distinguish conserved mechanisms from species-specific observations and identify opportunities for integrating renal transport physiology, toxicology, pharmacology, and regenerative biology. Collectively, teleost models provide an important platform for understanding aquatic adaptation and for generating mechanistic hypotheses relevant to mammalian renal pharmacology.